Bruton’s Tyrosine Kinase Is Required for TLR2 and TLR4-Induced TNF, but Not IL-6, Production

作者: Nicole J. Horwood , Theresa H. Page , John P. McDaid , Christine D. Palmer , Jamie Campbell

DOI: 10.4049/JIMMUNOL.176.6.3635

关键词:

摘要: Bruton's tyrosine kinase (Btk), the gene mutated in human immunodeficiency X-linked agammaglobulinemia, is activated by LPS and required for LPS-induced TNF production. In this study, we have investigated role of Btk both signaling via another TLR (TLR2) production other proinflammatory cytokines such as IL-1beta, IL-6, IL-8. Our data show that agammaglobulinemia PBMCs, stimulation with TLR4 (LPS) or TLR2 (N-palmitoyl-S-[2, 3-bis(palmitoyloxy)-(2R)-propyl]-(R)-cysteine) ligands produces significantly less IL-1beta than normal controls. contrast, a lack has no impact on IL-8, anti-inflammatory cytokine, IL-10. previous suggested lies within p38-dependent pathway stabilizes mRNA. Accordingly, TaqMan quantitative PCR analysis actinomycin D time courses presented work shows overexpression able to stabilize TNF, but not IL-6 Furthermore, using p38 inhibitor SB203580, TLR4-induced requires activity MAPK. These provide evidence common requirement TLR2- TLR4-mediated induction two important cytokines, reveal differences TLR-mediated signals

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