| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,,
Departments of
*
Pediatrics and
Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada;
Division of Virology and Molecular Immunology, Research Institute, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada;
Division of Infectious Diseases, Department of Medicine, Vancouver Hospital, University of British Columbia, Vancouver, British Columbia, Canada; and
¶ Health Canada, Therapeutic Products Program, Research Services Division, Ottawa, Ontario, Canada
The costimulatory molecule B7.2 (CD86) plays a vital role in immune
activation and development of Th responses. The molecular mechanisms by
which B7.2 expression is regulated are not understood. We investigated
the role of mitogen-activated protein kinases (MAPK) in the regulation
of B7.2 expression in LPS-stimulated human monocytic cells. LPS
stimulation of human monocytes resulted in the down-regulation of B7.2
expression that could be abrogated by anti-IL-10 Abs. Furthermore,
SB202190, a specific inhibitor of p38 MAPK, inhibited LPS-induced IL-10
production and reversed B7.2 down-regulation, suggesting that
LPS-induced B7.2 down-regulation may be mediated, at least in part, via
regulation of IL-10 production by p38 MAPK. In contrast to human
promonocytic THP-1 cells that are refractory to the inhibitory
effects of IL-10, LPS stimulation enhanced B7.2 expression. This
IL-10-independent B7.2 induction was not influenced by specific
inhibitors of either p38 or p42/44 MAPK. To ascertain the role of the
c-Jun N-terminal kinase (JNK) MAPK, dexamethasone, an inhibitor of JNK
activation, was used, which inhibited LPS-induced B7.2 expression.
Transfection of THP-1 cells with a plasmid expressing a
dominant-negative stress-activated protein/extracellular
signal-regulated kinase kinase 1 significantly reduced
LPS-induced B7.2 expression, thus confirming the involvement of JNK. To
study the signaling events downstream of JNK activation, we show that
dexamethasone did not inhibit LPS-induced NF-
B activation in THP-1
cells, suggesting that JNK may not be involved in NF-B activation
leading to B7.2 expression. Taken together, our results reveal the
distinct involvement of p38 in IL-10-dependent, and JNK in
IL-10-independent regulation of B7.2 expression in LPS-stimulated
monocytic cells.
This article has been cited by other articles:
|
|
 |
|
  J. Liang, J. Wang, A. Azfer, W. Song, G. Tromp, P. E. Kolattukudy, and M. Fu A Novel CCCH-Zinc Finger Protein Family Regulates Proinflammatory Activation of Macrophages J. Biol. Chem., March 7, 2008; 283(10): 6337 - 6346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Salojin and T. Oravecz Regulation of innate immunity by MAPK dual-specificity phosphatases: knockout models reveal new tricks of old genes J. Leukoc. Biol., April 1, 2007; 81(4): 860 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Kim, V. Rajagopal, C. Gonsalves, C. Johnson, and V. K. Kalra A Novel Role of Hypoxia-Inducible Factor in Cobalt Chloride- and Hypoxia-Mediated Expression of IL-8 Chemokine in Human Endothelial Cells J. Immunol., November 15, 2006; 177(10): 7211 - 7224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Taggart, S.-A. Cryan, S. Weldon, A. Gibbons, C. M. Greene, E. Kelly, T. B. Low, S. J. O'Neill, and N. G. McElvaney Secretory leucoprotease inhibitor binds to NF-{kappa}B binding sites in monocytes and inhibits p65 binding J. Exp. Med., December 19, 2005; 202(12): 1659 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bracci-Laudiero, L. Aloe, M. C. Caroleo, P. Buanne, N. Costa, G. Starace, and T. Lundeberg Endogenous NGF regulates CGRP expression in human monocytes, and affects HLA-DR and CD86 expression and IL-10 production Blood, November 15, 2005; 106(10): 3507 - 3514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Lim, K. Gee, S. Mishra, and A. Kumar Regulation of B7.1 Costimulatory Molecule Is Mediated by the IFN Regulatory Factor-7 through the Activation of JNK in Lipopolysaccharide-Stimulated Human Monocytic Cells J. Immunol., November 1, 2005; 175(9): 5690 - 5700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. R. Rahimi, K. Gee, S. Mishra, W. Lim, and A. Kumar STAT-1 Mediates the Stimulatory Effect of IL-10 on CD14 Expression in Human Monocytic Cells J. Immunol., June 15, 2005; 174(12): 7823 - 7832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Vanlandschoot, F. Van Houtte, P. Ulrichts, J. Tavernier, and G. Leroux-Roels Immunostimulatory potential of hepatitis B nucleocapsid preparations: lipopolysaccharide contamination should not be overlooked J. Gen. Virol., February 1, 2005; 86(2): 323 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nakahara, H. Uchi, K. Urabe, Q. Chen, M. Furue, and Y. Moroi Role of c-Jun N-terminal kinase on lipopolysaccharide induced maturation of human monocyte-derived dendritic cells Int. Immunol., December 1, 2004; 16(12): 1701 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Farina, D. Theil, B. Semlinger, R. Hohlfeld, and E. Meinl Distinct responses of monocytes to Toll-like receptor ligands and inflammatory cytokines Int. Immunol., June 1, 2004; 16(6): 799 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. W. Verreck, T. de Boer, D. M. L. Langenberg, M. A. Hoeve, M. Kramer, E. Vaisberg, R. Kastelein, A. Kolk, R. de Waal-Malefyt, and T. H. M. Ottenhoff Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria PNAS, March 30, 2004; 101(13): 4560 - 4565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ma, K. Gee, W. Lim, K. Chambers, J. B. Angel, M. Kozlowski, and A. Kumar Dexamethasone Inhibits IL-12p40 Production in Lipopolysaccharide-Stimulated Human Monocytic Cells by Down-Regulating the Activity of c-Jun N-Terminal Kinase, the Activation Protein-1, and NF-{kappa}B Transcription Factors J. Immunol., January 1, 2004; 172(1): 318 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Selvaraj, R. K. Giri, N. Perelman, C. Johnson, P. Malik, and V. K. Kalra Mechanism of monocyte activation and expression of proinflammatory cytochemokines by placenta growth factor Blood, August 15, 2003; 102(4): 1515 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Martin, S. M. Michalek, and J. Katz Role of Innate Immune Factors in the Adjuvant Activity of Monophosphoryl Lipid A Infect. Immun., May 1, 2003; 71(5): 2498 - 2507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Morichika, H. K. Takahashi, H. Iwagaki, T. Yoshino, R. Tamura, M. Yokoyama, S. Mori, T. Akagi, M. Nishibori, and N. Tanaka Histamine Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-{alpha} Production in an Intercellular Adhesion Molecule-1- and B7.1-Dependent Manner J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 624 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Gee, W. Lim, W. Ma, D. Nandan, F. Diaz-Mitoma, M. Kozlowski, and A. Kumar Differential Regulation of CD44 Expression by Lipopolysaccharide (LPS) and TNF-{alpha} in Human Monocytic Cells: Distinct Involvement of c-Jun N-Terminal Kinase in LPS-Induced CD44 Expression J. Immunol., November 15, 2002; 169(10): 5660 - 5672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Creery, J. B. Angel, S. Aucoin, W. Weiss, W. D. Cameron, F. Diaz-Mitoma, and A. Kumar Nef Protein of Human Immunodeficiency Virus and Lipopolysaccharide Induce Expression of CD14 on Human Monocytes through Differential Utilization of Interleukin-10 Clin. Vaccine Immunol., November 1, 2002; 9(6): 1212 - 1221. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
