| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
CUTTING EDGE |
Promoter in Primary CD4+ T Lymphocytes1
*
Laboratory of Immunology, I. Medical Clinic, and
Institute of Immunology, University of Mainz, Mainz, Germany
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
promoter in primary
human CD4+ T cells. In transfection experiments, we
found that IL-18 directly induces IFN- promoter activity, whereas
significant activation with IL-12 required costimulation with
CD3/CD28. Furthermore, IL-12 caused in vivo protection of a STAT4
(-236) binding site, whereas stimulation with IL-18 or IL-12 plus
CD3/CD28 induced occupancy of a downstream AP-1 site. Mutation of
this AP-1 site abrogated both IL-12- and IL-18-mediated promoter
activation, whereas mutation of the STAT site inhibited IL-12-dependent
activation. These data suggest that both AP-1 and STAT4 are required
for IL-12-dependent IFN- promoter activity, whereas IL-18 causes
direct activation via AP-1. This differential activation of the IFN-
promoter gives further insights into molecular pathways governing Th1 T
cell development and differentiation. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
from T and NK cells by binding to its
specific receptor. While the ß2 chain of the IL-12 receptor is
expressed only in Th1 T cells, the ß1 chain is expressed in both Th1
and Th2 T cells. Thus, it is the expression of both the ß1 and ß2
chains that accounts for the responsiveness of T cells to IL-12 and
mediates Th1 T cell differentiation (4, 5, 6). On binding to its receptor,
IL-12 induces activation of specific members of the STAT family of
transcription factors (STAT3 and STAT4), which then translocate to the
nucleus and bind to genomic promoter regions, including that governing
IFN- (7, 8). STAT4 is particularly important in this respect, as
shown by the fact that STAT4-deficient T cells manifest impaired
production of IFN-. In addition, the phenotype of the IL-12 p40
deficient mouse is similar to that of the STAT4-deficient mouse
(8, 9, 10).
IL-18, designated also IFN--inducing factor
(IGIF),3 is a recently cloned
cytokine of 18.3 kDa the production of which is restricted to
phagocytic cells (11). IL-18 strongly augments IFN- production by T
cells, NK cell cytotoxicity, and T cell proliferation. Previous studies
in T cell clones showed that recombinant IL-18 induces IFN-
production more potently than does IL-12 (12). Interestingly, recent
reports revealed that IL-12 and IL-18 exert a synergistic effect on
IFN- production in T cells (13). It was suggested that one of the
possible molecular mechanisms underlying this synergy consists of the
induction of IGIF receptor by IL-12, thereby enhancing IL-18
responsiveness of T cells.
In this report, we examined the differential effects of IL-18 and IL-12
on IFN- production in primary T cells at the transcriptional level.
We found that while IL-18 directly induces high IFN- promoter
activity, IL-12 exhibits activating function only in the presence of
costimulatory signals provided by CD3/28 Abs. Furthermore, we
identified differential molecular target sites at the IFN- promoter
that were associated with IL-12 or IL-18 responsiveness of primary
CD4+ T cells.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Freshly isolated CD4+ T cells were cultured in RPMI 1640 supplemented with 10% FCS (PAA, Linz, Austria), 5% NCTC 135 medium (Life Technologies, Gaithersburg, MD), 20 mM HEPES buffer (Life Technologies), 2 mM L-glutamine (Life Technologies), and 1000 U/ml penicillin/streptomycin (Biochrom, Berlin, Germany).
Isolation of CD4+ T lymphocytes
Human PBMC were isolated from healthy volunteers using Ficoll-Hypaque (Pharmacia, Piscataway, NJ) gradients. Immunomagnetic beads specific for CD4+ (obtained from Dynal, Oslo, Norway) were then used to isolate CD4+ T cells (14). The beads were finally removed from the cells by treatment with Detachabead (Dynal). Only cell populations with a purity of >95% were used in the experiments described below. The cells were cultured in a humidified atmosphere with 5% CO2 in a 37°C incubator.
Stimulation of CD4+ T cells
Cells were stimulated with anti-human CD3 Ab (Cat. No. 30110D, PharMingen, San Diego, CA), anti-human CD28 Ab (Cat. No. 33740D, PharMingen), recombinant human IL-12 (p70, Cat. No. 19721 V, PharMingen), and IL-18 (Cat. No. 200–18, Peprotech, Rocky Hill, NJ). Anti-CD3 and CD28 Abs were directly added to the cells at a concentration of 1 µg/ml.
ELISA for IFN-
Primary CD4+ T lymphocytes
(106/well) were seeded out in triplicate in 48-well tissue
culture plates and incubated at 37°C in the presence or absence of
different stimuli as indicated in Stimulation of
CD4+ T cells. After 48 h, cell-free
culture supernatants were removed and assayed for IFN- concentration
by ELISA as described (14).
Dimethyl sulfate (DMS)-piperidine treatment of DNA for in vivo footprinting and ligation-mediated PCR (LM-PCR)
Cells were methylated with 0.1% DMS and lysed overnight in cell lysis buffer (14). After extraction of DNA with phenol/chloroform, the methylated DNA was precipitated, and the strand scission reaction was performed in 1 M piperidine. In vivo footprinting by LM-PCR was performed with 0.5 pmol of primer 1 for 1 µg of genomic DMS and piperidine-treated DNA (15). After primer extension with Sequenase 1.0 (United States Biochemical, Cleveland, OH), the linker ligation reaction was performed overnight at 15°C. Exponential PCR amplification was done with primer 2 and the linker primer for 15 to 22 cycles (94°C for 1 min, melting temperature + 1°C for 2 min, 76°C for 3 min). Finally, the 32P-labeled third primer was added together with 2 U of Taq DNA polymerase and 2 µl of deoxynucleotide triphosphates (5 mM each), and a final PCR cycle was performed, followed by DNA analysis on a 5% denaturing urea/polyacrylamide gel. Primer sequences for LM-PCR: 1, 5'-gctgatcttcagatgatcag-3'; 2, 5'-agaacaatgtgctgcacctcctctg-3'; 3, 5'-atgtgctgcacctcctctggctgct-3'.
Reporter gene analysis
An IFN- promoter fragment (-572 to +7) was amplified by PCR
from Jurkat T cell genomic DNA (upstream primer
5'-ccctttgtaaaggtttgagaggccc-3', downstream primer
5'-atgtgctgcacctcctctggc-3'). The 397-bp IFN- promoter fragment was
cloned into the pCRII vector (Invitrogen, Leek, the Netherlands) by TA
cloning. The IFN- promoter DNA was then excised with
EcoRI from the pCRII vector, treated with mung bean nuclease
(Amersham, Amersham, Arlington Heights, IL), and cloned into the
SmaI site of the promoterless pXP1 luciferase reporter gene
vector. Ten micrograms of this pXP-IFN- vector were transfected into
1 x 107 CD4+ T cells using the DEAE
transfection method. After 24 h the cells were stimulated for
18 h as described in Stimulation of
CD4+ T cells, harvested, washed in PBS, and
lysed in cell lysis buffer (Promega, Madison, WI). Luciferase activity
was measured as light emission over a period of 10 s after
addition of luciferase assay buffer (Promega) with a scintillation
counter (Top Count, Packard, Meriden, CT). Data were normalized for
transfection efficiency by galactosidase activity using the pSV-ßgal
reporter plasmid system (Cat. No. 6047-1, Clontech, Heidelberg,
Germany).
Site-directed mutagenesis
Site-directed mutagenesis was performed with the Quickchange Site-Directed Mutagenesis Kit (Stratagene, Heidelberg, Germany, Cat. No. 200518) according to the manufacturer’s instructions. Primer sequences were as follows (mutagenized nucleotides are underlined, and deletions are marked by an asterisk): AP-1 mut, 5'-ATG GGT CTG TAT CAT CGT CAA AGG A-3'; 3'-TAC CCA GAC ATA GTA GCA GTT TCC T-5'. STAT mut, 5'-AGT CCT TGA ATG GTG TGA AGT AAA AGT GCC *TCA AAC AAT CCC C-3'; 5'-TCA GGA ACT TAC CAC ACT TCA TTT TCA CGG *AGT TTG TTA GGG G-3'.
Electrophoretic mobility shift assay (EMSA)
Nuclear proteins were isolated as described (16).
Oligonucleotides for EMSA were end-labeled with
[-32P]ATP (>5000 Ci/mmol, Amersham) using T4
polynucleotide kinase (New England Biolabs, Beverly, MA). For
supershift assays, 2 µg of rabbit anti-human c-Jun/AP-1 Ab (Santa
Cruz Biotechnology, Santa Cruz, CA) was used. The binding reaction was
incubated at room temperature for 30 min. After electrophoresis, the
gels were dried and exposed to Kodak MS films on intensifiying screens
at -80°C. The sequences of the oligonucleotides for EMSA were as
follows: AP-1, IFN- 5'-ATG GGT CTG TCT CAT CGT CAA AGG A-3'; 3'-TAC
CCA GAC AGA GTA GCA GTT TCC T-3'. STAT, 5'-AGT CCT TGA ATG GTG TGA AGT
AAA AGT GCC TTC AAA GAA T CC CC-3'; 5'-TCA GGA ACT TAC CAC ACT TCA TTT
TCA CGG AAG T TT CTT AGG GG-3'.
EMSA gels were analyzed by densitometry using a PhosphorImager system (Molecular Dynamics, Sunnyvale, CA).
Statistical analysis
Data from transfection experiments were analyzed by the Wilcoxon test using the program Statworks for MacIntosh.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
promoter activity
and IFN- protein production in primary human CD4+
T cells
Previous studies demonstrated that whereas IL-18 (IGIF) exerts
significant IFN--inducing activity in human PBMC (11), IL-12 favors
Th1 T cell differentiation by priming CD4+ T cells for
high IFN- production (1). To examine the specific effects of both
cytokines on IFN- induction in human CD4+ T cells, we
performed ELISAs using supernatants from IL-12- and IL-18-stimulated
primary CD4+ T cells. rIL-18 (IGIF) markedly stimulated
IFN- protein production by human CD4+ T cells (Fig. 1
A). In contrast,
IFN- production of CD4+ T cells was not strongly induced by IL-12
treatment alone (Fig. 1B).
|
induction in human T lymphocytes, we
constructed a plasmid containing the wild-type IFN- promoter
sequence (positions -572 to +7) upstream of a luciferase reporter
gene. By transient transfection experiments with the resulting
construct, denoted pXP-IFN-, we then determined IFN- promoter
activity in primary T cells. In this experimental system, IL-18 alone
was a potent inducer of IFN- promoter activity in primary
CD4+ T cells, while IL-12 alone did not have a significant
effect on reporter gene activity (Fig. 2). However, in the presence of
costimulatory signals provided by soluble Abs to CD3 and CD28, IL-12
strongly induced IFN- promoter activity in primary CD4+
T cells.
|
promoter identifies different
molecular targets elements for IL-12 and IL-18
In additional experiments, we determined potential molecular
target sites for IL-12 and IL-18 at the IFN- promoter by in vivo DNA
footprinting via LM-PCR. Accordingly, we isolated methylated DNA from
unstimulated and stimulated CD4+ T cells and subjected
the DNA to the LM-PCR procedure (see Materials and
Methods). An altered in vivo DMS reactivity in
IL-18-stimulated CD4+ T cells was found at an AP-1 binding
site at -190 (Fig. 3) that was recently
characterized in our laboratory as a critical element for IFN-
promoter activity in primary CD4+ T cells (14). In
contrast, activation of CD4+ T cells via IL-12 did not
induce altered DMS reactivity over this AP-1 site but at a recently
described STAT binding site (19) suggesting IL-12-dependent protein
binding to this site in vivo. However, activation of T cells with IL-12
plus CD3/28 led to an altered DMS reactivity over the downstream
AP-1 binding site as observed with IL-18 alone.
|
In further studies, we assessed the inducibility of the
AP-1-binding complex in nuclear extracts from primary human
CD4+ T cells in response to IL-12 and IL-18. As shown
in Figure 4A, AP-1 binding
activity was highly inducible by IL-18 (>20-fold) and CD3/28 plus
IL-12 treatment, but not by IL-12 application alone. Furthermore, IL-18
caused a dose-dependent increase of AP-1 binding activity and IFN-
mRNA production by Jurkat T cells (data not shown). Interestingly,
supershift experiments showed that c-jun Abs cause a supershift of the
AP-1 band in IL-12 plus CD3/28, but not in IL-12-stimulated
CD4+ T cells suggesting that induction of c-jun
is important for IL-12 plus CD3/28-dependent IFN- promoter
activity (Fig. 4B). Finally, we found that
stimulation of CD4+ T cells with IL-12 or IL-12 plus
CD3/28 induced binding of STAT4 to the STAT site of the IFN-
promoter (Fig. 4C). In contrast, this complex was not
found after stimulation with IL-18 suggesting that IL-12 but not IL-18
induces STAT4 activation in primary CD4+ T lymphocytes.
|
promoter activation
To determine the functional importance of the AP-1 and STAT sites
for IL-12- and IL-18-dependent IFN- promoter activity, we performed
transient transfection assays in CD4+ T cells.
Accordingly, we constructed mutagenized plasmids containing deletions
or mutations of the AP-1 and STAT sites of the IFN- promoter that
are known to prevent protein binding to these sites (14, 17). As shown
in Figure 5, transfection of an AP-1
mutant IFN- promoter construct in primary CD4+ T cells
significantly (p < 0.01) reduced reporter gene
activity in both IL-12- and IL-18-stimulated T cells compared with the
wild-type construct. However, mutation of the STAT site caused only a
slight inhibition of IL-18-induced promoter activity but a highly
significant (p < 0.01) reduction in
IL-12-dependent promoter activity.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
is a fundamental property of Th1
cells in various infectious and autoimmune diseases (1, 19). IL-18 and
IL-12 strongly enhance IFN- production of CD4+ T
cells and are capable of acting in a synergistic fashion (11, 13). The
data reported here show that that IL-12 and IL-18 act differentially to
activate IFN- gene transcription in primary human CD4+ T
cells. Furthermore, they suggest that both AP-1 and STAT4 are required
for IL-12-dependent IFN- promoter activation, whereas IL-18 causes
direct promoter activation via AP-1. This differential activation of
the IFN- promoter gives further insights into molecular pathways
governing Th1 T cell development and differentiation.
In initial ELISA and transient transfection experiments, we showed that
both IL-12 and IL-18 are capable of inducing IFN- promoter activity.
However, whereas IL-18 stimulation alone strongly enhanced IFN-
promoter activity, promoter activation via IL-12 required costimulatory
signals provided by soluble CD3/28 Abs. These data in primary T
cells are consistent with data from the work of Jacobson et al. (7)
showing that IL-12 alone does not activate IFN- promoter activity in
murine EL-4 T cell lines. In further studies, we identified various
cis-responsive elements for IL-12 and IL-18 at the IFN-
promoter. We found an intense footprint in IL-18-stimulated T cells
over an AP-1 sequence element at -190 that plays a critical role in
inducible activity of the IFN- promoter in primary T cells (14).
Mutagenesis of this AP-1 element abrogated IFN- promoter activation
by IL-18 and IL-12 plus CD3/CD28, indicating that this site is
absolutely required for both IL-12- and IL-18-mediated promoter
activation. Thus, although there are various other important
cis-regulatory elements at the IFN- promoter that are
involved in the regulation of its activity (20, 21, 22, 23, 24, 25), these data suggest
that AP-1 plays a crucial role in mediating both IL-12- and
IL-18-dependent IFN- promoter activity in primary human
CD4+ T-cells.
Further studies of the IFN- promoter regulation in primary T cells
showed in vivo occupation of a recently characterized STAT binding site
(24) at position -236 of the transcriptional start site. Whereas the
identification of this STAT binding site was based on in vitro binding
assays, our genomic footprinting and transfection data indicate for the
first time functional importance of this STAT binding site for
mediating IL-12 effects in primary CD4+ T cells in vivo.
Previous studies have shown that IL-12 induces STAT3/4 tyrosine
phosphorylation and finally nuclear STAT-binding
activity in T cells (7). Consistent with this model, our results
indicate that IL-12 stimulation of CD4+ T cells induces
STAT binding to its target DNA sequence at -236 in the IFN-
promoter in vivo. Interestingly, however, such binding seems to be
required but not sufficient to induce high IFN- promoter activity in
primary CD4+ T cells. However, after IL-12 plus CD3/28
stimulation a footprint over the downstream AP-1 site (-190) of the
IFN- promoter was found the appearance of which strongly correlated
with high IFN- promoter activity and IFN- protein production.
Interestingly, mutation of either the STAT or the AP-1 site
abrogated IL-12 plus CD3/28 effects on IFN- promoter activity,
suggesting that both sites are absolutely required for this stimulation
condition.
The data reported here provide evidence that IFN- gene transcription
in primary CD4+ T cells is differentially modulated by
IL-12 and IL-18 (Fig. 6). Whereas IL-18
activates directly the IFN- promoter by recruitment of AP-1
binding, IL-12 stimulation induces STAT4 binding but requires
costimulatory signals provided by CD3/28 Abs to activate IFN-
promoter activity via STAT/AP-1. Thus, regulation of AP-1 and STAT
binding activities emerges as a key event in controlling the
transcriptional activity of the human IFN- promoter in
CD4+ T lymphocytes.
|
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Markus F. Neurath, Laboratory of Immunology, I. Medical Clinic, University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
3 Abbreviations used in this paper: IGIF, interferon--inducing factor; LM-PCR, ligation-mediated PCR; DMS, dimethyl sulfate; EMSA, electrophoretic mobility shift assay.
Received for publication December 22, 1997. Accepted for publication February 18, 1998.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
ß-TCR transgenic CD4+ T cells occurs through macrophage production of IL-12. Science 260:547.-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein. J. Immunol. 156:4274.[Abstract]
production by T cells. Nature 378:88.[Medline]
production and activates IRAK and NF
B. Immunity 7:571.[Medline]
promoter in vivo in CD45RA and CD45RO T helper subsets. Eur. J. Immunol. 27:1098.[Medline]
enhancer by affecting binding of NF-P, a protein that controls heavy chain transcription. Proc. Natl. Acad. Sci. USA 92:5336.B abrogates experimental colitis in mice. Nat. Med. 2:998.[Medline]
This article has been cited by other articles:
|
|
 |
|
  A. Sattler, U. Wagner, M. Rossol, J. Sieper, P. Wu, A. Krause, W. A. Schmidt, S. Radmer, S. Kohler, C. Romagnani, et al. Cytokine-induced human IFN-{gamma}-secreting effector-memory Th cells in chronic autoimmune inflammation Blood, February 26, 2009; 113(9): 1948 - 1956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Desy, D. Carignan, M. Caruso, and P. O. de Campos-Lima Immunosuppressive Effect of Isopropanol: Down-Regulation of Cytokine Production Results from the Alteration of Discrete Transcriptional Pathways in Activated Lymphocytes J. Immunol., August 15, 2008; 181(4): 2348 - 2355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Lebre, S. L. Jongbloed, S. W. Tas, T. J.M. Smeets, I. B. McInnes, and P. P. Tak Rheumatoid Arthritis Synovium Contains Two Subsets of CD83-DC-LAMP- Dendritic Cells with Distinct Cytokine Profiles Am. J. Pathol., April 1, 2008; 172(4): 940 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Athie-Morales, G. M. O'Connor, and C. M. Gardiner Activation of Human NK Cells by the Bacterial Pathogen-Associated Molecular Pattern Muramyl Dipeptide J. Immunol., March 15, 2008; 180(6): 4082 - 4089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Marusina, S. J. Burgess, I. Pathmanathan, F. Borrego, and J. E. Coligan Regulation of Human DAP10 Gene Expression in NK and T Cells by Ap-1 Transcription Factors J. Immunol., January 1, 2008; 180(1): 409 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sun, S. Lee, S. Karray, M. Levi-Strauss, K. T. Ames, and P. J. Fink Cutting Edge: Two Distinct Motifs within the Fas Ligand Tail Regulate Fas Ligand-Mediated Costimulation J. Immunol., November 1, 2007; 179(9): 5639 - 5643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Trotta, D. Ciarlariello, J. D. Col, J. Allard II, P. Neviani, R. Santhanam, H. Mao, B. Becknell, J. Yu, A. K. Ferketich, et al. The PP2A inhibitor SET regulates natural killer cell IFN-{gamma} production J. Exp. Med., October 1, 2007; 204(10): 2397 - 2405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Smeltz Profound Enhancement of the IL-12/IL-18 Pathway of IFN-{gamma} Secretion in Human CD8+ Memory T Cell Subsets via IL-15 J. Immunol., April 15, 2007; 178(8): 4786 - 4792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Hildner, P. Schirmacher, I. Atreya, M. Dittmayer, B. Bartsch, P. R. Galle, S. Wirtz, and M. F. Neurath Targeting of the Transcription Factor STAT4 by Antisense Phosphorothioate Oligonucleotides Suppresses Collagen-Induced Arthritis J. Immunol., March 15, 2007; 178(6): 3427 - 3436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Becknell, T. L. Hughes, A. G. Freud, B. W. Blaser, J. Yu, R. Trotta, H. C. Mao, M. L. Caligiuri de Jesus, M. Alghothani, D. M. Benson Jr, et al. Hlx homeobox transcription factor negatively regulates interferon-{gamma} production in monokine-activated natural killer cells Blood, March 15, 2007; 109(6): 2481 - 2487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Suto, A. L. Wurster, S. L. Reiner, and M. J. Grusby IL-21 Inhibits IFN-{gamma} Production in Developing Th1 Cells through the Repression of Eomesodermin Expression J. Immunol., September 15, 2006; 177(6): 3721 - 3727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Moreno, J. C. Alves-Filho, T. M. Alfaya, J. S. da Silva, S. H. Ferreira, and F. Y. Liew IL-12, but Not IL-18, Is Critical to Neutrophil Activation and Resistance to Polymicrobial Sepsis Induced by Cecal Ligation and Puncture. J. Immunol., September 1, 2006; 177(5): 3218 - 3224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. MacGregor, Q. Li, A. E. Chang, T. M. Braun, D. P.M. Hughes, and K. T. McDonagh Ex vivo Culture with Interleukin (IL)-12 Improves CD8+ T-Cell Adoptive Immunotherapy for Murine Leukemia Independent of IL-18 or IFN-{gamma} but Requires Perforin. Cancer Res., May 1, 2006; 66(9): 4913 - 4921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tanaka, M. Sato, T. Onitsuka, H. Kamata, and Y. Yokomizo Inflammatory Cytokine Gene Expression in Different Types of Granulomatous Lesions during Asymptomatic Stages of Bovine Paratuberculosis Vet. Pathol., September 1, 2005; 42(5): 579 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Takahashi, H. Iwagaki, D. Xue, G. Katsuno, S. Sugita, K. Mizuno, S. Mori, S. Saito, T. Yoshino, N. Tanaka, et al. Effect of Ciprofloxacin-Induced Prostaglandin E2 on Interleukin-18-Treated Monocytes Antimicrob. Agents Chemother., August 1, 2005; 49(8): 3228 - 3233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Pages, J. Galon, G. Karaschuk, D. Dudziak, M. Camus, V. Lazar, S. Camilleri-Broet, C. Lagorce-Pages, S. Lebel-Binay, G. Laux, et al. Epstein-Barr virus nuclear antigen 2 induces interleukin-18 receptor expression in B cells Blood, February 15, 2005; 105(4): 1632 - 1639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Schleicher, A. Hesse, and C. Bogdan Minute numbers of contaminant CD8+ T cells or CD11b+CD11c+ NK cells are the source of IFN-{gamma} in IL-12/IL-18-stimulated mouse macrophage populations Blood, February 1, 2005; 105(3): 1319 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kusaba, P. Ghosh, R. Derin, M. Buchholz, C. Sasaki, K. Madara, and D. L. Longo Interleukin-12-induced Interferon-{gamma} Production by Human Peripheral Blood T Cells Is Regulated by Mammalian Target of Rapamycin (mTOR) J. Biol. Chem., January 14, 2005; 280(2): 1037 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mavropoulos, G. Sully, A. P. Cope, and A. R. Clark Stabilization of IFN-{gamma} mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells Blood, January 1, 2005; 105(1): 282 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gonsky, R. L. Deem, J. Bream, H. A. Young, and S. R. Targan Enhancer Role of STAT5 in CD2 Activation of IFN-{gamma} Gene Expression J. Immunol., November 15, 2004; 173(10): 6241 - 6247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Morinobu, Y. Kanno, and J. J. O'Shea Discrete Roles for Histone Acetylation in Human T Helper 1 Cell-specific Gene Expression J. Biol. Chem., September 24, 2004; 279(39): 40640 - 40646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Bream, D. L. Hodge, R. Gonsky, R. Spolski, W. J. Leonard, S. Krebs, S. Targan, A. Morinobu, J. J. O'Shea, and H. A. Young A Distal Region in the Interferon-{gamma} Gene Is a Site of Epigenetic Remodeling and Transcriptional Regulation by Interleukin-2 J. Biol. Chem., September 24, 2004; 279(39): 41249 - 41257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Akhiani, K. Schon, and N. Lycke Vaccine-Induced Immunity against Helicobacter pylori Infection Is Impaired in IL-18-Deficient Mice J. Immunol., September 1, 2004; 173(5): 3348 - 3356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Cunard, Y. Eto, J. T. Muljadi, C. K. Glass, C. J. Kelly, and M. Ricote Repression of IFN-{gamma} Expression by Peroxisome Proliferator-Activated Receptor {gamma} J. Immunol., June 15, 2004; 172(12): 7530 - 7536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Chitnis, A. D. Salama, M. J. Grusby, M. H. Sayegh, and S. J. Khoury Defining Th1 and Th2 Immune Responses in a Reciprocal Cytokine Environment In Vivo J. Immunol., April 1, 2004; 172(7): 4260 - 4265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Stallmach, T Marth, B Weiss, B M Wittig, A Hombach, C Schmidt, M Neurath, M Zeitz, S Zeuzem, and H Abken An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn's disease and experimental colitis in vivo Gut, March 1, 2004; 53(3): 339 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Finotto, J Siebler, M Hausding, M Schipp, S Wirtz, S Klein, M Protschka, A Doganci, H A Lehr, C Trautwein, et al. Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for IL-18 in regulating hepatocyte apoptosis in vivo Gut, March 1, 2004; 53(3): 392 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O'Sullivan, H.-C. Chang, Q. Yu, and M. H. Kaplan STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus J. Biol. Chem., February 20, 2004; 279(8): 7339 - 7345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-R. Park, M. Nakahira, N. Sugimoto, Y. Bian, Y. Yashiro-Ohtani, X.-Y. Zhou, Y.-F. Yang, T. Hamaoka, and H. Fujiwara A mechanism underlying STAT4-mediated up-regulation of IFN-{gamma} induction inTCR-triggered T cells Int. Immunol., February 1, 2004; 16(2): 295 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-H. Chiang, L. Wang, C. A. Bonham, X. Liang, J. J. Fung, L. Lu, and S. Qian Mechanistic Insights into Impaired Dendritic Cell Function by Rapamycin: Inhibition of Jak2/Stat4 Signaling Pathway J. Immunol., February 1, 2004; 172(3): 1355 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Durali, M.-G. de Goer de Herve, J. Giron-Michel, B. Azzarone, J.-F. Delfraissy, and Y. Taoufik In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment Blood, December 1, 2003; 102(12): 4084 - 4089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Monick, L. Samavati, N. S. Butler, M. Mohning, L. S. Powers, T. Yarovinsky, D. R. Spitz, and G. W. Hunninghake Intracellular Thiols Contribute to Th2 Function via a Positive Role in IL-4 Production J. Immunol., November 15, 2003; 171(10): 5107 - 5115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Freudenberg, C. Kalis, Y. Chvatchko, T. Merlin, M. Gumenscheimer, and C. Galanos Role of interferons in LPS hypersensitivity Innate Immunity, October 1, 2003; 9(5): 308 - 312. [Abstract] [PDF]
|
|
|
|
|
|
J. Wang, R. A. Barke, R. Charboneau, H. H. Loh, and S. Roy Morphine Negatively Regulates Interferon-{gamma} Promoter Activity in Activated Murine T Cells through Two Distinct Cyclic AMP-dependent Pathways J. Biol. Chem., September 26, 2003; 278(39): 37622 - 37631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Bream, R. E. Curiel, C.-R. Yu, C. E. Egwuagu, M. J. Grusby, T. M. Aune, and H. A. Young IL-4 synergistically enhances both IL-2- and IL-12-induced IFN-{gamma} expression in murine NK cells Blood, July 1, 2003; 102(1): 207 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ito, A. Matejuk, C. Hopke, H. Drought, J. Dwyer, A. Zamora, S. Subramanian, A. A. Vandenbark, and H. Offner Transfer of Severe Experimental Autoimmune Encephalomyelitis by IL-12- and IL-18-Potentiated T Cells Is Estrogen Sensitive J. Immunol., May 1, 2003; 170(9): 4802 - 4809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Gracie, S. E. Robertson, and I. B. McInnes Interleukin-18 J. Leukoc. Biol., February 1, 2003; 73(2): 213 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Strengell, T. Sareneva, D. Foster, I. Julkunen, and S. Matikainen IL-21 Up-Regulates the Expression of Genes Associated with Innate Immunity and Th1 Response J. Immunol., October 1, 2002; 169(7): 3600 - 3605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Morinobu, M. Gadina, W. Strober, R. Visconti, A. Fornace, C. Montagna, G. M. Feldman, R. Nishikomori, and J. J. O'Shea STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation PNAS, September 17, 2002; 99(19): 12281 - 12286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. M. Morel, C. C. Park, K. Zhu, P. Kumar, J. H. Ruth, and A. E. Koch Signal Transduction Pathways Involved in Rheumatoid Arthritis Synovial Fibroblast Interleukin-18-induced Vascular Cell Adhesion Molecule-1 Expression J. Biol. Chem., September 13, 2002; 277(38): 34679 - 34691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Freudenberg, T. Merlin, C. Kalis, Y. Chvatchko, H. Stubig, and C. Galanos Cutting Edge: A Murine, IL-12-Independent Pathway of IFN-{gamma} Induction by Gram-Negative Bacteria Based on STAT4 Activation by Type I IFN and IL-18 Signaling J. Immunol., August 15, 2002; 169(4): 1665 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Takahashi, H. Iwagaki, T. Yoshino, S. Mori, T. Morichika, H. Itoh, M. Yokoyama, S. Kubo, E. Kondo, T. Akagi, et al. Prostaglandin E2 Inhibits IL-18-Induced ICAM-1 and B7.2 Expression Through EP2/EP4 Receptors in Human Peripheral Blood Mononuclear Cells J. Immunol., May 1, 2002; 168(9): 4446 - 4454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Singh, S.-i. Kashiwamura, P. Rao, H. Okamura, A. Mukherjee, and V. S. Chauhan The Role of IL-18 in Blood-Stage Immunity Against Murine Malaria Plasmodium yoelii265 and Plasmodium bergheiANKA J. Immunol., May 1, 2002; 168(9): 4674 - 4681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Hodge, A. Martinez, J. G. Julias, L. S. Taylor, and H. A. Young Regulation of Nuclear Gamma Interferon Gene Expression by Interleukin 12 (IL-12) and IL-2 Represents a Novel Form of Posttranscriptional Control Mol. Cell. Biol., March 15, 2002; 22(6): 1742 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Whitman, P. Ravisankar, and A. Daugherty Interleukin-18 Enhances Atherosclerosis in Apolipoprotein E-/- Mice Through Release of Interferon-{gamma} Circ. Res., February 8, 2002; 90 (2): e34 - e38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V M Salvati, T T MacDonald, M Bajaj-Elliott, M Borrelli, A Staiano, S Auricchio, R Troncone, and G Monteleone Interleukin 18 and associated markers of T helper cell type 1 activity in coeliac disease Gut, February 1, 2002; 50(2): 186 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakahira, H.-J. Ahn, W.-R. Park, P. Gao, M. Tomura, C.-S. Park, T. Hamaoka, T. Ohta, M. Kurimoto, and H. Fujiwara Synergy of IL-12 and IL-18 for IFN-{gamma} Gene Expression: IL-12-Induced STAT4 Contributes to IFN-{gamma} Promoter Activation by Up-Regulating the Binding Activity of IL-18-Induced Activator Protein 1 J. Immunol., February 1, 2002; 168(3): 1146 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wirtz, C. Becker, R. Blumberg, P. R. Galle, and M. F. Neurath Treatment of T Cell-Dependent Experimental Colitis in SCID Mice by Local Administration of an Adenovirus Expressing IL-18 Antisense mRNA J. Immunol., January 1, 2002; 168(1): 411 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Curiel, C. S. Garcia, L. Farooq, M. F. Aguero, and I. Espinoza-Delgado Bryostatin-1 and IL-2 Synergize to Induce IFN-{gamma} Expression in Human Peripheral Blood T Cells: Implications for Cancer Immunotherapy J. Immunol., November 1, 2001; 167(9): 4828 - 4837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Esfandiari, I. B. McInnes, G. Lindop, F.-P. Huang, M. Field, M. Komai-Koma, X.-q. Wei, and F. Y. Liew A Proinflammatory Role of IL-18 in the Development of Spontaneous Autoimmune Disease J. Immunol., November 1, 2001; 167(9): 5338 - 5347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Siegmund, G. Fantuzzi, F. Rieder, F. Gamboni-Robertson, H.-A. Lehr, G. Hartmann, C. A. Dinarello, S. Endres, and A. Eigler Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-gamma and TNF-alpha production Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2001; 281(4): R1264 - R1273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Becker, S. Wirtz, X. Ma, M. Blessing, P. R. Galle, and M. F. Neurath Regulation of IL-12 p40 Promoter Activity in Primary Human Monocytes: Roles of NF-{kappa}B, CCAAT/Enhancer-Binding Protein {beta}, and PU.1 and Identification of a Novel Repressor Element (GA-12) That Responds to IL-4 and Prostaglandin E2 J. Immunol., September 1, 2001; 167(5): 2608 - 2618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Trobonjaca, F. Leithauser, P. Moller, R. Schirmbeck, and J. Reimann Activating Immunity in the Liver. I. Liver Dendritic Cells (but Not Hepatocytes) Are Potent Activators of IFN-{gamma} Release by Liver NKT Cells J. Immunol., August 1, 2001; 167(3): 1413 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Harandi, B. Svennerholm, J. Holmgren, and K. Eriksson Interleukin-12 (IL-12) and IL-18 Are Important in Innate Defense against Genital Herpes Simplex Virus Type 2 Infection in Mice but Are Not Required for the Development of Acquired Gamma Interferon-Mediated Protective Immunity J. Virol., July 15, 2001; 75(14): 6705 - 6709. [Abstract] [Full Text]
|
|
|
|
|
|
D. Stober, R. Schirmbeck, and J. Reimann IL-12/IL-18-Dependent IFN-{{gamma}} Release by Murine Dendritic Cells J. Immunol., July 15, 2001; 167(2): 957 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Chuang, H.-T. K. Pham, P. R. Kumaresan, and P. A. Mathew A Prominent Role for Activator Protein-1 in the Transcription of the Human 2B4 (CD244) Gene in NK Cells J. Immunol., May 15, 2001; 166(10): 6188 - 6195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yao, J. Setsuda, C. Sgadari, B. Cherney, and G. Tosato Interleukin-18 expression induced by Epstein-Barr virus-infected cells J. Leukoc. Biol., May 1, 2001; 69(5): 779 - 784. [Abstract] [Full Text]
|
|
|
|
|
|
G. S. Yap, R. Ortmann, E. Shevach, and A. Sher A Heritable Defect in IL-12 Signaling in B10.Q/J Mice. II. Effect on Acute Resistance to Toxoplasma gondii and Rescue by IL-18 Treatment J. Immunol., May 1, 2001; 166(9): 5720 - 5725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Walter, N. Kajiwara, P. Karanja, M. Castro, and M. J. Holtzman Interleukin 12 P40 Production by Barrier Epithelial Cells during Airway Inflammation J. Exp. Med., February 5, 2001; 193(3): 339 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Leite-de-Moraes, A. Hameg, M. Pacilio, Y. Koezuka, M. Taniguchi, L. Van Kaer, E. Schneider, M. Dy, and A. Herbelin IL-18 Enhances IL-4 Production by Ligand-Activated NKT Lymphocytes: A Pro-Th2 Effect of IL-18 Exerted Through NKT Cells J. Immunol., January 15, 2001; 166(2): 945 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hyun Kim, L. L. Reznikov, R. J. L. Stuyt, C. H. Selzman, G. Fantuzzi, T. Hoshino, H. A. Young, and C. A. Dinarello Functional Reconstitution and Regulation of IL-18 Activity by the IL-18R{beta} Chain J. Immunol., January 1, 2001; 166(1): 148 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Lawless, S. Zhang, O. N. Ozes, H. A. Bruns, I. Oldham, T. Hoey, M. J. Grusby, and M. H. Kaplan Stat4 Regulates Multiple Components of IFN-{gamma}-Inducing Signaling Pathways J. Immunol., December 15, 2000; 165(12): 6803 - 6808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Airoldi, G. Gri, J. D. Marshall, A. Corcione, P. Facchetti, R. Guglielmino, G. Trinchieri, and V. Pistoia Expression and Function of IL-12 and IL-18 Receptors on Human Tonsillar B Cells J. Immunol., December 15, 2000; 165(12): 6880 - 6888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Debets, J. C. Timans, T. Churakowa, S. Zurawski, R. de Waal Malefyt, K. W. Moore, J. S. Abrams, A. O'Garra, J. F. Bazan, and R. A. Kastelein IL-18 Receptors, Their Role in Ligand Binding and Function: Anti-IL-1RAcPL Antibody, a Potent Antagonist of IL-18 J. Immunol., November 1, 2000; 165(9): 4950 - 4956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Kitching, P. G. Tipping, M. Kurimoto, and S. R. Holdsworth IL-18 Has IL-12-Independent Effects in Delayed-Type Hypersensitivity: Studies in Cell-Mediated Crescentic Glomerulonephritis J. Immunol., October 15, 2000; 165(8): 4649 - 4657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Greene, G. Meachery, C. C. Taggart, C. P. Rooney, R. Coakley, S. J. O'Neill, and N. G. McElvaney Role of IL-18 in CD4+ T Lymphocyte Activation in Sarcoidosis J. Immunol., October 15, 2000; 165(8): 4718 - 4724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Salkowski, K. E. Thomas, M. J. Cody, and S. N. Vogel Impaired IFN-{gamma} Production in IFN Regulatory Factor-1 Knockout Mice During Endotoxemia Is Secondary to a Loss of Both IL-12 and IL-12 Receptor Expression J. Immunol., October 1, 2000; 165(7): 3970 - 3977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhang and M. H. Kaplan The p38 Mitogen-Activated Protein Kinase Is Required for IL-12-Induced IFN-{gamma} Expression J. Immunol., August 1, 2000; 165(3): 1374 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Glimcher and K. M. Murphy Lineage commitment in the immune system: the T helper lymphocyte grows up Genes & Dev., July 15, 2000; 14(14): 1693 - 1711. [Full Text]
|
|
|
|
|
|
T.-K. Yu, E. G. Caudell, C. Smid, and E. A. Grimm IL-2 Activation of NK Cells: Involvement of MKK1/2/ERK But Not p38 Kinase Pathway J. Immunol., June 15, 2000; 164(12): 6244 - 6251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Labuda, A. Sundstedt, and M. Dohlsten Selective induction of p38 mitogen-activated protein kinase activity following A6H co-stimulation in primary human CD4+ T cells Int. Immunol., March 1, 2000; 12(3): 253 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tominaga, T. Yoshimoto, K. Torigoe, M. Kurimoto, K. Matsui, T. Hada, H. Okamura, and K. Nakanishi IL-12 synergizes with IL-18 or IL-1{beta} for IFN-{gamma} production from human T cells Int. Immunol., February 1, 2000; 12(2): 151 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kaisho, H. Tsutsui, T. Tanaka, T. Tsujimura, K. Takeda, T. Kawai, N. Yoshida, K. Nakanishi, and S. Akira Impairment of Natural Killer Cytotoxic Activity and Interferon {gamma} Production in Ccaat/Enhancer Binding Protein {gamma}-Deficient Mice J. Exp. Med., December 6, 1999; 190(11): 1573 - 1582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Zhang, T. Nakamura, and T. M. Aune TCR and IL-12 Receptor Signals Cooperate to Activate an Individual Response Element in the IFN-{gamma} Promoter in Effector Th Cells J. Immunol., July 15, 1999; 163(2): 728 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Walker, M. Aste-Amezaga, R. A. Kastelein, G. Trinchieri, and C. A. Hunter IL-18 and CD28 Use Distinct Molecular Mechanisms to Enhance NK Cell Production of IL-12-Induced IFN-{gamma} J. Immunol., May 15, 1999; 162(10): 5894 - 5901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. E. Garcia, K. Uyemura, P. A. Sieling, M. T. Ochoa, C. T. Morita, H. Okamura, M. Kurimoto, T. H. Rea, and R. L. Modlin IL-18 Promotes Type 1 Cytokine Production from NK Cells and T Cells in Human Intracellular Infection J. Immunol., May 15, 1999; 162(10): 6114 - 6121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kojima, Y. Aizawa, Y. Yanai, K. Nagaoka, M. Takeuchi, T. Ohta, H. Ikegami, M. Ikeda, and M. Kurimoto An Essential Role for NF-{kappa}B in IL-18-Induced IFN-{gamma} Expression in KG-1 Cells J. Immunol., May 1, 1999; 162(9): 5063 - 5069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Fehniger, M. H. Shah, M. J. Turner, J. B. VanDeusen, S. P. Whitman, M. A. Cooper, K. Suzuki, M. Wechser, F. Goodsaid, and M. A. Caligiuri Differential Cytokine and Chemokine Gene Expression by Human NK Cells Following Activation with IL-18 or IL-15 in Combination with IL-12: Implications for the Innate Immune Response J. Immunol., April 15, 1999; 162(8): 4511 - 4520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kanakaraj, K. Ngo, Y. Wu, A. Angulo, P. Ghazal, C. A. Harris, J. J. Siekierka, P. A. Peterson, and W.-P. Fung-Leung Defective Interleukin (IL)-18-mediated Natural Killer and T Helper Cell Type 1 Responses in IL-1 Receptor-associated Kinase (IRAK)-deficient Mice J. Exp. Med., April 5, 1999; 189(7): 1129 - 1138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ouyang, N. G. Jacobson, D. Bhattacharya, J. D. Gorham, D. Fenoglio, W. C. Sha, T. L. Murphy, and K. M. Murphy The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway PNAS, March 30, 1999; 96(7): 3888 - 3893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Claesson, S. Bregenholt, K. Bonhagen, S. Thoma, P. Moller, M. J. Grusby, F. Leithauser, M. H. Nissen, and J. Reimann Colitis-Inducing Potency of CD4+ T Cells in Immunodeficient, Adoptive Hosts Depends on Their State of Activation, IL-12 Responsiveness, and CD45RB Surface Phenotype J. Immunol., March 15, 1999; 162(6): 3702 - 3710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pardoux, X. Ma, S. Gobert, S. Pellegrini, P. Mayeux, F. Gay, G. Trinchieri, and S. Chouaib Downregulation of Interleukin-12 (IL-12) Responsiveness in Human T Cells by Transforming Growth Factor-beta : Relationship With IL-12 Signaling Blood, March 1, 1999; 93(5): 1448 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wirtz, S. Finotto, S. Kanzler, A. W. Lohse, M. Blessing, H. A. Lehr, P. R. Galle, and M. F. Neurath Cutting Edge: Chronic Intestinal Inflammation in STAT-4 Transgenic Mice: Characterization of Disease and Adoptive Transfer by TNF- Plus IFN-{gamma}-Producing CD4+ T Cells That Respond to Bacterial Antigens J. Immunol., February 15, 1999; 162(4): 1884 - 1888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Car, V. M. Eng, J. M. Lipman, and T. D. Anderson The Toxicology of Interleukin-12: A Review Toxicol Pathol, January 1, 1999; 27(1): 58 - 63. [Abstract] [PDF]
|
|
|
|
|
|
M. T. Sweetser, T. Hoey, Y.-L. Sun, W. M. Weaver, G. A. Price, and C. B. Wilson The Roles of Nuclear Factor of Activated T Cells and Ying-Yang 1 in Activation-induced Expression of the Interferon-gamma Promoter in T Cells J. Biol. Chem., December 25, 1998; 273(52): 34775 - 34783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Ehret, P. Reichenbach, U. Schindler, C. M. Horvath, S. Fritz, M. Nabholz, and P. Bucher DNA Binding Specificity of Different STAT Proteins. COMPARISON OF IN VITRO SPECIFICITY WITH NATURAL TARGET SITES J. Biol. Chem., February 23, 2001; 276(9): 6675 - 6688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Whitman, P. Ravisankar, and A. Daugherty Interleukin-18 Enhances Atherosclerosis in Apolipoprotein E-/- Mice Through Release of Interferon-{gamma} Circ. Res., February 8, 2002; 90 (2): e34 - e38. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
, protected G residues. Bottom, Shorter
exposure of the same gel as above in the AP-1 area. The E-site is an
E-Box element of the IFN-
