| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1
*
Departament de Fisiologia (Immunologia), Facultat de Biologia and Fundacio August Pi i Sunyer, Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain; and
Basel Institute for Immunology, Basel, Switzerland and Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas, Madrid, Spain
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
). IFN-
increases the surface expression of class II molecules in a murine B
cell line without inducing detectable changes in either I-A or I-A mRNA
levels. In bone marrow-derived M, IFN- causes an increase in
class II expression at both the mRNA and surface levels. In addition to
the increase in transcription rates described for M, IFN-
increases the rate of synthesis of IA
and IAß proteins and the
ribosome loading for both mRNA molecules in both cell types.
Interestingly, there is a significant peak of free I-A mRNA in
noninduced cells. Therefore, IFN- regulates the expression of MHC
class II molecules at the translational level in both B cells and M
and, as already reported, at the transcriptional level only in M.
The actual mechanism of regulation causes changes in the translation
initiation rates in both cell types, as demonstrated by an increase in
ribosome loading in polysome gradients. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Class II proteins are expressed on a limited set of cell types, which
include B lymphocytes, thymic epithelial cells, glial cells, dendritic
cells, and macrophages
(M)3. Activated human T
cells also express class II molecules but do not express their murine
counterparts (4). The expression of class II molecules is regulated by
cytokines, mainly IFN- (5) and IL-4 (6), primarily through
transcriptional activation (7). However, little work has been reported
on the posttranscriptional events that take place under these
circumstances.
mRNA stability does not play a significant role in
IFN--induced MHC II expression (Ref. 8; M. Cullell-Young, E.
Goñalons, and A. Celada, manuscript in preparation). Therefore,
in this report we have focused on the translational events that take
place upon IFN- stimulation of both B cells and M. Translational
control has been described for a variety of systems (reviewed in Refs.
9 and 10). This control can be a general event consisting of the
phosphorylation of the protein factors involved in the translational
process (11) or can take place through highly specific mechanisms. The
latter include events at the level of elongation (12, 13) or at
the termination phase, such as the frame shifting described in
the expression of many viral proteins, but also in some
mammalian mRNAs (14). However, most translationally
controlled mRNAs are regulated at the initiation step by multiple
specific mechanisms (15).
In the present study, we demonstrate that IFN- is a translational
activator of MHC class II Ag expression. In murine B lymphocytes,
IFN- increases I-A surface expression, but the levels of IA and
IAß mRNAs remain unchanged. In M, the observed increase takes
place both at the mRNA and the surface expression levels. In both cell
types, independently of the transcriptional effects, IFN- increases
the binding of ribosomes to I-A mRNAs, thus increasing the translation
rates of MHC class II molecules.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Bone marrow-derived M (BMDMs) were obtained as described
previously (16). Briefly, 6- to 8-wk-old C3H/HeJ mice (Charles
River Laboratories, Wilmington, MA) were killed by cervical
dislocation, and both femurs were dissected free of adherent tissue.
The ends of the bones were cut off, and the marrow tissue was eluted by
irrigation with culture media. The cells were desegregated by
passing the suspension several times through an 18-gauge needle. The
cells were then plated in 150-mm petri dishes in 40 ml of high-glucose
DMEM containing 20% FCS (Sigma, St. Louis, MO) and 30% L
cell-conditioned media as a source of M CSF. The cells were cultured
at 37°C in a humidified 5% CO2 atmosphere for 7 to 8
days until reaching confluence. The murine lymphoma A20 cell line was
also used (17). A20 cells were maintained in high-glucose DMEM
supplemented with 50 M 2-ME and 5% FCS.
IFN-
For IFN- stimulation studies, saturating amounts (300 U/ml)
of murine rIFN- (18) were added to the media for the indicated
times. The cytokine was a kind gift from Genentech, Inc. (South San
Francisco, CA).
Antibodies
For the surface staining of MHC class II molecules, we used Ab
11-5.2.1.9 (anti-I-Ak, PharMingen, San Diego, CA) for
M and 34-5-3 (anti-I-Ad, PharMingen) for A20 B
cells. In both cases, FITC-labeled sheep anti-mouse IgG (Cappel,
Turnhout, Belgium) was used as a secondary Ab. To block FcRs, we used
anti-CD16/CD32 Ab (PharMingen). For the immunoprecipitation
experiments we used, rabbit antiserum FF282–4 as anti-I-A (19)
and 10-2.16 Ab (20) as anti-I-Aß. The anti-I-A antiserum
was kindly provided by Dr. R. N. Germain (National Institutes of
Health, Bethesda, MD), and the anti-I-Aß Ab was provided by Dr.
P. Cosson (Basel Institute for Immunology, Basel, Switzerland). These
Abs were chosen for their ability to recognize I-A and ß subunits
independently of their association (21). For the immunoprecipitation of
ß-actin we used mouse anti-mouse ß-actin AC-15 Ab (Sigma).
Determination of cell surface expression of I-A molecules
Cell surface staining was conducted using specific Abs and cytofluorometric analysis as described previously (22). Cells were washed in PBS and resuspended in 100 µl of PBS containing 5% FCS. Next, they were incubated at 4°C with 1 µg/106 cells of anti-CD16/CD32 mAb to block FcRs. After 15 min, the primary Ab was added, and the cells were further incubated for 45 min at 4°C. The cells were then washed by centrifugation through an FCS cushion. Finally, they were incubated with fluorescein-conjugated secondary Ab for 45 min at 4°C. Cytometry analysis was conducted using an Epics XL (Coulter, Miami, FL) apparatus or a FACScan apparatus (Becton Dickinson, Bedford, MA).
RNA blot analysis
Northern blotting, slot blotting, and RNase protection techniques were used for the analysis of polysome gradients. For Northern blotting, one-fifth of each fraction of the gradient or 30 µg of total RNA were electrophoretically separated in a 1.2% agarose/formaldehyde gel. The RNA was then transferred by capillarity onto a nylon membrane (GeneScreen, DuPont, Boston, MA). For slot blotting, one-fifth of each fraction of the gradient was applied to the membrane in 5x SSC, 20 mM Tris-HCl (pH 7.5), and 18.5% formaldehyde using a vacuum manifold (Minifold II, Schleicher and Schuell, Dassel, Germany). Hybridization was conducted overnight in 50% formamide at 65°C for riboprobes and 42°C for cDNA probes (23).
RNase protection assay
A fragment of I-Aßk cDNA (21) ranging from
position 1 to 230 of the open reading frame was used for the analysis
of I-Aß RNA. For I-A, we used a fragment of I-Ak
cDNA (21) covering positions 1 to 489 of the open reading frame. I-A
and I-Aß cDNAs were a kind gift of Dr. P. Cosson. Both fragments were
subcloned into the pGEM3 vector (Promega, Madison, WI). As a control,
we used a PstI (1)-BglII (173) fragment of mouse
ß-actin cDNA (24).
Labeled RNA that was complementary to the mRNA was generated in all cases from the SP6 promoter using SP6 polymerase. Probe synthesis, hybridization, digestion, and acrylamide gel electrophoresis of the protected probe were performed as described previously (25). Quantification of the bands was conducted using a Molecular Imaging System (Bio-Rad, Hercules, CA) and a PhosphorImager (Molecular Dynamics, Sunnyvale, CA).
Metabolic labeling and immunoprecipitations
The cells were biosynthetically labeled for 20 min with 500
µCi/ml of [35S]Met/Cys mix (Pro-mix
L-[35S]) in vivo cell-labeling mix, Amersham,
Buckinghamshire, U.K.) in methionine-free DMEM supplemented with 10%
dialyzed FCS. Next, the cells were collected and washed once with
ice-cold PBS. The cell pellet was lysed in 1 ml of lysis buffer (3.6
mg/ml iodoacetamide, 150 mM NaCl, 50 mM Tris-HCl (pH 7.4), 0.5% Triton
X-100, 5 µg/ml aprotinin, 0.2 mM PMSF, and 20 µg/ml leupeptin) on
ice for 15 min. The lysate was centrifuged for 15 min at 12,000 x
g at 4°C. The protein concentration was assessed by the
Bradford method, and equal amounts of protein from IFN--treated and
untreated cells were used for the immunoprecipitations. I-A and
I-Aß were immunoprecipitated from separate samples using specific Abs
coated to protein G. The immunocomplexes were then washed three times
in buffer containing 150 mM NaCl, 50 mM Tris-HCl (pH 7.4), and 0.1%
Triton X-100; resuspended in Laemmli buffer (65 mM Tris-HCl (pH 6.8),
2% SDS, 0.7 M ß2-ME, and 10% glycerol); and boiled for 5 min. The
samples were subjected to electrophoresis on 12% SDS-polyacrylamide
gels; the gels were processed for autoradiography. Quantification of
the radioactivity in the bands was conducted by direct counting of the
gel slices in a scintillation counter.
Polysome gradients
The cells were collected and washed in ice-cold PBS. The pellet
was resuspended in 1 ml of lysis buffer (10 mM Tris-HCl (pH 8), 150 mM
NaCl, 1.5 mM MgCl2, and 0.5% v/v Nonidet P-40)
supplemented with 10 µl of RNase inhibitor (RNAguard, Pharmacia
Biotech, Uppsala, Sweden). The cell lysate was centrifuged for 2 min at
3000 x g at 4°C. The supernatant was then
transferred to a new tube containing heparin to 0.6 µg/ml,
cycloheximide to 0.15 µg/ml, DTT to 20 mM, and PMSF to 1 mM. Finally,
the lysate was centrifuged again for 5 min at 4°C; loaded onto a 10
ml linear 15 to 40% sucrose gradient that had been prepared as
described previously (26) in 10 mM Tris-HCl (pH 7.5), 140 mM NaCl, and
1.5 mM MgCl2; and centrifuged for 3 h at 28,000 rpm in
a Beckman SW28.1 (Fullerton, CA). Fractions of 
550
µl were collected into tubes containing SDS to 1%, EDTA (pH 8) to 10
mM, and proteinase K to 200 µg/ml. The fractions were incubated for
30 min at 37°C followed by phenol/chloroform extraction and ethanol
precipitation. The specific mRNA content of each fraction was analyzed
by Northern blotting, slot blotting, or the RNase protection assay. The
position of ribosomes in the gradient was assessed by hybridization
with a 28S ribosomal RNA (rRNA) probe. To ensure that the denser
fractions contained polysome-bound mRNA, we prepared sucrose gradients
in which the 1.5 mM MgCl2 had been substituted with 10 mM
EDTA. In all cases, the mRNA accumulated in the top fractions (data not
shown), which indicates that the mRNAs migrating to denser fractions
are polysome-bound.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
is the strongest inducer of the expression of MHC class II
molecules in cells of the M lineage (27). Moreover, previous work
has suggested that IFN- also induces the expression of these Ags in
B lymphocytes (28). In our studies, we used the mature B cell line A20,
which is devoid of any M characteristics (17). A20 cells
constitutively express MHC class II I-A molecules on the cell surface;
after stimulation with IFN-, the surface expression of MHC class II
molecules increased two- to threefold over basal conditions (Fig. 1
A) Interestingly, this
increase in I-A surface expression was not accompanied by changes at
the mRNA steady-state levels of either and ß I-A chains, as
determined by Northern blotting using either total or cytoplasmic RNA
(Fig. 1B and data not shown). This finding suggests that the
effect of IFN- on the surface levels of I-A molecules is not due to
a different distribution of the messenger between the nucleus and the
cytoplasm.
|
-specific Abs able to recognize I-A chains
independent of the presence of I-Aß and/or invariant chains (Iis)
(p31 and p41), a two- to threefold increase in the translation rate of
I-A protein was detected (mean of three different experiments) (Fig. 2) The translation rates of I-Aß and
Iis were not quantified, since it has not been demonstrated whether the
Abs used were able to recognize these proteins independently of their
association to I-A. As a control, we used an anti-ß-actin Ab
(Fig. 2).
|
treatment
despite inducing an increase in the rate of I-A protein synthesis
suggested a translational control for this mRNA; several mechanisms may
be responsible for this control. For most of the examples known,
initiation is the step during which translation is controlled. To
analyze translational control at the initiation step, polysome
gradients were performed; the profiles of I-A and I-Aß mRNAs were
analyzed both before and after IFN- treatment. The fractioning of
the cellular mRNAs in a sucrose gradient allows the separation of free
mRNA from mRNA that is bound to one or more ribosomes. In noninduced B
lymphocytes, I-Aß mRNA was bound to several ribosomes, but I-A
mRNA displayed quite a large peak of mRNA (60%) in the fractions
devoid of ribosomes, indicating that this quantity of I-A mRNA was
not being translated (Fig. 3,
top). After 48 h of IFN- treatment, there was a
shift toward the polysome bound-fractions for both mRNAs; this shift
was particularly important in the case of I-A, which showed a marked
reduction (from 60–35%) in the unbound mRNA peak. These data
indicated that IFN- induced an increase in the translation of MHC
class II molecules in B lymphocytes, causing the dissociation between
the levels of mRNA and the protein synthesis rate. As controls, the
distribution of 28S rRNA and ß-actin mRNA were used (Fig. 3).
|
,
a cell type in which the expression of class II molecules is inducible.
For this purpose we used BMDMs, which represent a homogeneous
population of nontransformed, quiescent cells.
Using the RNase protection assay with haplotype-specific probes, we
observed that M expressed very low levels of both I-A and I-Aß
mRNAs under basal conditions. Incubating BMDMs with
saturating amounts of IFN- induced a slow increase in mRNA levels
that started as late as 8 to 12 h after the treatment and reached
a plateau after 48 h (Fig. 4) From
then on, the mRNA levels stayed high and constant for at least 24
h. We observed a marked difference between the levels of expression
achieved by I-A and I-Aß mRNAs. I-A reached a maximum increase
in the level of expression of 10 to 12-fold compared with that in
untreated cells, whereas I-Aß reached about twice that much (an
increase of 25–30-fold). At the cell surface level, BMDMs showed
increased I-A expression upon IFN- stimulation. This increase in
mean fluorescence intensity reached 9- to 10-fold over a 48-h treatment
period (Fig. 5) and slowly decreased to
5-fold after 96 h of IFN- treatment (data not shown).
|
|
and I-Aß after
48 h of IFN- treatment in three independent experiments. For
this purpose, [35S] biosynthetically labeled cells were
lysed, and the cytoplasmic extracts were immunoprecipitated using
specific Abs against each of the two I-A chains. We found a 6- to
7-fold increase for I-A and a 15- to 17-fold increase for I-Aß
over basal levels. ß-actin was used as a control and did not show any
variation in its protein synthesis rate after 48 h of treatment
with IFN- (Fig. 6).
|
is able to modify the translation of I-A mRNAs in B
cells, we analyzed the effect of IFN- on the polysome gradient
profiles of I-A and I-Aß mRNAs in M. As seen in Figure 7, both mRNAs showed a profile in
noninduced cells in which 30% of the messenger was in free form and
the rest was evenly distributed along the ribosome-bound fraction
range. However, after IFN--stimulation, both mRNAs underwent a
marked shift toward polysome-bound mRNA, indicating that the treatment
induced an increase in the average number of ribosomes bound to these
specific mRNAs and, consequently, an increase in the efficiency of
protein synthesis. As a control, we used ß-actin, which did not show
any change in its distribution profile or in the mean number of
ribosomes attached per molecule of ß-actin mRNA. Finally, a general
decrease in total protein synthesis per cell was detected after 72
h of IFN- stimulation of the cells; this decrease is concomitant
with a shift of ß-actin mRNA toward the free mRNA fractions. However,
this general decrease of protein synthesis did not affect I-A mRNA,
which remained accumulated in the denser fractions, confirming the
presence of a specific mechanism responsible for the effect of IFN-
(Fig. 8).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
regulates the
expression of MHC class II molecules at the level of translation in
both B cell lines and primary M. An increase in the surface
expression of MHC class II molecules after IFN- stimulation has been
shown for M (27) as well as for B lymphocytes (28). The mechanism
underlying this effect has been described exclusively as an increased
mRNA expression. According to our results, this is not the case for
either M or B lymphocytes. Under our experimental conditions, we
have found increased I-A surface expression in B cells treated with
IFN- but no changes in the levels of I-A and I-Aß mRNAs.
Furthermore, we have found that IFN- does not alter the
t1/2 of I-A mRNAs; since the amount of mRNA is
the same, we conclude that this cytokine does not increase the level of
transcription of I-A mRNA. Therefore, there must be some
posttranscriptional event that can account for the increased MHC class
II surface expression. Another possibility is that IFN- increases
the transit of mRNA from the nucleus to the cytoplasm, thus increasing
the amount of mRNA available for translation; however, we have found
that IFN- does not significantly modify the amount of cytoplasmic
mRNA either. Finally, our data also showed that the protein synthesis
rate in B cells was increased by the IFN- treatment. Consistently,
the polysome gradient analyses that were performed showed that IFN-
induces both a shift of free I-A mRNA toward polysome-bound
fractions and an increase in the density of I-Aß mRNA in B
lymphocytes, indicating that there is an increase in translational
efficiency. Our study is not a unique case in which translation is the
only regulatory step, as the expression of other genes such as ferritin
(29) or insulin-like growth factor-II (30) is regulated only at this
level. The analysis of the polysome distribution profile of I-A and
I-Aß mRNA in B cells shows that I-Aß is mainly accumulated in the
polysome-bound fractions, whereas I-A shows a large peak of free
mRNA. Therefore, I-Aß is being actively translated, while the
translation of I-A is repressed. These data might seem to be in
disagreement with the fact that B cells show a constitutive expression
of MHC class II molecules. However, despite a peak of free mRNA, 40%
of I-A mRNA is still in the polysome-bound fractions which, when
added to the long t1/2 of MHC class II molecules
on the cell surface (8), would account for the maintenance of surface
protein turnover.
It has been well-established that MHC class II gene expression is
induced in M (27). Before IFN- treatment, we found low levels of
I-A mRNAs as well as I-A protein synthesis in these cells. This
observation is in agreement with previous models in which residual
amounts of class II expression were detected despite a lack of response
to IFN-, such as the targeted gene inactivation of class II
transactivator (31) or STAT-1 genes (32). In M,
IFN- not only increases the levels of class II mRNAs but also
increases their translational rates; this finding is in contrast to
that seen with B cells, in which this cytokine only acts at the
translational step. Also, the polysome gradients showed a marked shift
of both I-A and I-Aß mRNA from free toward polysome-bound mRNA in
IFN--treated M, indicating that IFN- also has effect on the
translational process in this case. In addition, IFNs have been shown
to induce a general decrease in protein synthesis through direct or
indirect mechanisms (33). Accordingly, ß-actin shows a partial shift
toward free mRNA at the 72-h timepoint, indicating a generalized
inhibition of protein synthesis. However, I-A mRNA stays bound to
ribosomes, thus confirming the specificity of translational induction
by IFN-. Reviewing our model, we must point out that existing data
(34) indicate the presence of a translational regulatory mechanism in
M. Also, Sicher et al. (35) have shown that LPS, acting as a second
signal after IFN- pretreatment, induces an increase in the surface
cell expression of MHC class II molecules without changing the mRNA
levels. Finally, our data with regard to B cells demonstrate that the
binding of mRNAs to ribosomes is not a process that is controlled by
the amount of mRNA present in the cell; rather, this process is
completely independent and is regulated by different mechanisms. In
accordance with this hypothesis, the results presented show that I-A
and I-Aß mRNAs have different polysome distribution profiles in B
lymphocytes, despite showing similar levels of expression.
The data in this work is in agreement with other studies that have
shown the relevance of translational regulation in the control of gene
expression in a variety of systems. For the past few years, growing
evidence has arisen regarding the role of translational processes as a
key step in the regulation of gene expression, and every day new genes
appear to be regulated at this level by mechanisms that are just as
complex as those involved in transcriptional regulation (36).
Translational machinery is controlled by several mechanisms that
regulate the various steps of the process. However, most mRNAs have
their expression modulated at the initiation phase by increasing the
binding of new ribosomes to the 5' end of the mRNA (15). Since treating
the cells with IFN- induces a change in the population of free mRNA,
inducing it to bind to ribosomes, we can conclude that initiation is
the step during which this cytokine exerts its effects in this case.
In conclusion, IFN- has a regulatory effect on the translation of
I-A molecules in both M and B cells; in the latter case, IFN- is
the only regulatory mechanism. These data provide evidence of a new
step in the regulation of the expression of MHC class II molecules by
IFN-.
|
Acknowledgments |
|---|
antiserum. We also thank
Dr. P. Cosson from the Basel Institute for Immunology (Basel,
Switzerland) for the anti-I-A Abs and the plasmids containing the
I-A and I-Aß cDNAs. |
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. A. Celada, Departament de Fisiologia (Immunologia), Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028 Barcelona, Spain. E-mail address:
3 Abbreviations used in this paper: M, macrophage(s); rRNA, ribosomal RNA; BMDM, bone marrow-derived macrophage; Ii, invariant chain.
Received for publication January 22, 1998. Accepted for publication April 15, 1998.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
does not affect MHC class II gene expression at the post-transcriptional level in a mouse macrophage cell line. Immunogenetics 30:258.[Medline]
-IFN receptor that regulates macrophage tumoricidal activity. J. Exp. Med. 160:55. receptor on human mononuclear phagocytes. J. Clin. Invest. 76:2196.
/ß-chains. J. Exp. Med. 174:799. induces the expression of the genes for MHC class II I-A ß and TNF through a protein kinase C-independent pathway. J. Immunol. 146:114.[Abstract]
and ß expression in immature thymocytes. Eur. J. Immunol. 24:1729.[Medline]
induces enhanced expression of Ia and H-2 antigens on B lymphoid, macrophage, and myeloid cell lines. J. Immunol. 131:788.[Abstract]
-induced MHC class II expression by lipopolysaccharides: the roles of TNF- and nitric oxide, and the importance of the sequence of signaling. J. Immunol. 155:5826.[Abstract]
This article has been cited by other articles:
|
|
 |
|
  E. Diaz-Guerra, R. Vernal, M. J. del Prete, A. Silva, and J. A. Garcia-Sanz CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells J. Immunol., December 1, 2007; 179(11): 7352 - 7357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Casals, M. Barrachina, M. Serra, J. Lloberas, and A. Celada Lipopolysaccharide Up-Regulates MHC Class II Expression on Dendritic Cells through an AP-1 Enhancer without Affecting the Levels of CIITA J. Immunol., May 15, 2007; 178(10): 6307 - 6315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Heo, T. K. Mondal, D. Gao, J. Kasten-Jolly, H. Kishikawa, and D. A. Lawrence Posttranscriptional Inhibition of Interferon-Gamma Production by Lead Toxicol. Sci., March 1, 2007; 96(1): 92 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yamauchi, C. Kim, S. Li, C. C. Marchal, J. Towe, S. J. Atkinson, and M. C. Dinauer Rac2-Deficient Murine Macrophages Have Selective Defects in Superoxide Production and Phagocytosis of Opsonized Particles J. Immunol., November 15, 2004; 173(10): 5971 - 5979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Heller, S. Matsukura, S. N. Georas, M. R. Boothby, P. B. Rothman, C. Stellato, and R. P. Schleimer Interferon-{gamma} Inhibits STAT6 Signal Transduction and Gene Expression in Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 573 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lekmine, S. Uddin, A. Sassano, S. Parmar, S. M. Brachmann, B. Majchrzak, N. Sonenberg, N. Hay, E. N. Fish, and L. C. Platanias Activation of the p70 S6 Kinase and Phosphorylation of the 4E-BP1 Repressor of mRNA Translation by Type I Interferons J. Biol. Chem., July 18, 2003; 278(30): 27772 - 27780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ilangumaran, D. Finan, J. La Rose, J. Raine, A. Silverstein, P. De Sepulveda, and R. Rottapel A Positive Regulatory Role for Suppressor of Cytokine Signaling 1 in IFN-{gamma}-Induced MHC Class II Expression in Fibroblasts J. Immunol., November 1, 2002; 169(9): 5010 - 5020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xaus, M. Comalada, M. Barrachina, C. Herrero, E. Gonalons, C. Soler, J. Lloberas, and A. Celada The Expression of MHC Class II Genes in Macrophages Is Cell Cycle Dependent J. Immunol., December 1, 2000; 165(11): 6364 - 6371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. MIKULITS, B. PRADET-BALADE, B. HABERMANN, H. BEUG, J. A. GARCIA-SANZ, and E. W. MÜLLNER Isolation of translationally controlled mRNAs by differential screening FASEB J, August 1, 2000; 14(11): 1641 - 1652. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. L. Johnson and L. A. Ball Induction and Maintenance of Autonomous Flock House Virus RNA1 Replication J. Virol., October 1, 1999; 73(10): 7933 - 7942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wojciechowski, J. DeSanctis, E. Skamene, and D. Radzioch Attenuation of MHC Class II Expression in Macrophages Infected with Mycobacterium bovis Bacillus Calmette-Guerin Involves Class II Transactivator and Depends on the Nramp1 Gene J. Immunol., September 1, 1999; 163(5): 2688 - 2696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xaus, M. Mirabet, J. Lloberas, C. Soler, C. Lluis, R. Franco, and A. Celada IFN-{gamma} Up-Regulates the A2B Adenosine Receptor Expression in Macrophages: A Mechanism of Macrophage Deactivation J. Immunol., March 15, 1999; 162(6): 3607 - 3614. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
