BIRB 796 has Distinctive Anti-inflammatory Effects on Different Cell Types
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
The pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin (IL)-1β are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-κB) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.
Abstract
The pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin (IL)-1β are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-κB) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.
참고문헌 (23)
- Feldmann, M., "Role of cytokines in rheumatoid arthritis", Annu. Rev. Immunol, 14, pp.397~440 (1996)
- Jarvis, B., "Etanercept: a review of its use in rheumatoid arthritis", Drugs, 57, pp.945~966 (1999)
- Weinblatt, M. E., "A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate", N. Engl. J. Med, 340, pp.253~259 (1999)
- Dinarello, C. A., "Interleukin-18 and the treatment of rheumatoid arthritis", Rheum. Dis. Clin. North. Am, 30, pp.417~434 (2004)
- Schafer, P. H., "T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-alpha production in a manner distinct from LPS activation of monocytes", J. Immunol, 162, pp.659~668 (1999)
- Debnath, J., "rlk", TXK encodes two forms of a novel cysteine string tyrosine kinase activated by Src family kinases, 1999, pp.19, 1498~1507
- Mendelson, K. G., "Independent regulation of JNK", p38 mitogen-activated protein kinases by metabolic oxidative stress in the liver, 1996, pp.93, 12908~12913
- Lee, J. C., "Inhibition of monocyte IL-1 production by the anti-inflammatory compound, SK&F 86002", Int. J. Immunopharmacol, 10, pp.835~843 (1988)
- Pargellis, C., "Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site", Nat. Struct. Biol, 9, pp.268~272 (2002)
- Branger, J., "Anti-inflammatory effects of a p38 mitogen- activated protein kinase inhibitor during human endotoxemia", J. Immunol, 168, pp.4070~4077 (2002)
- Branger, J., "Inhibition of coagulation, fibrinolysis, and endothelial cell activation by a p38 mitogen-activated protein kinase inhibitor during human endotoxemia", Blood, 101, pp.4446~4448 (2003)
- van den Blink, B., "P38 mitogen activated protein kinase is involved in the downregulation of granulocyte CXC chemokine receptors 1 and 2 during human endotoxemia", J. Clin. Immunol, 24, pp.37~41 (2004)
- Ono, K., "The p38 signal transduction pathway: activation and function", Cell. Signal, 12, pp.1~13 (2000)
- Kumar, S., "p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases", Nat. Rev. Drug Discov, 2, pp.717~726 (2003)
- Sundell, C. L., "AGI-1067: a multifunctional phenolic antioxidant, lipid modulator, anti-inflammatory and antiatherosclerotic agent", J. Pharmacol. Exp. Ther, 305, pp.1116~1123 (2003)
- Kuma, Y., "BIRB796 inhibits all p38MAPK isoforms in vitro and in vivo", J. Biol. Chem, 280, pp.19472~19479 (2005)
- Luyendyk, J. P., "A novel class of antioxidants inhibit LPS induction of tissue factor by selective inhibition of the activation of ASK1 and MAP kinases", Arterioscler. Thromb. Vasc. Biol, 27, pp.1857~1863 (2007)
- Choy, E. H., "Cytokine pathways and joint inflammation in rheumatoid arthritis", N. Engl. J. Med, 344, pp.907~916 (2001)
- Lee, J. C., "A protein kinase involved in the regulation of inflammatory cytokine biosynthesis", Nature, 372, pp.739~746 (1994)
- Hanks, S. K., "The protein kinase family: conserved features and deduced phylogeny of the catalytic domains", Science, 241, pp.42~52 (1988)
- Hale, K. K., "Differential expression and activation of p38 mitogen- activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages", J. Immunol, 162, pp.4246~4252 (1999)
- Uddin, S., "Differentiation stage-specific activation of p38 mitogen-activated protein kinase isoforms in primary human erythroid cells", Proc. Natl. Acad. Sci. U. S. A, 101, pp.147~152 (2004)
- Hsu, H. Y., "Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression", J. Biol. Chem, 277, pp.22131~22139 (2002)