PHARMACOLOGICAL ANALYSIS OF SIGNAL TRANSDUCTION PATHWAYS REQUIRED FOR MYCOBACTERIUM TUBERCULOSIS -INDUCED IL-8 AND MCP-1 PRODUCTION IN HUMAN PERIPHERAL MONOCYTES

摘要: Signalling cascades involved in chemokine production by human phagocytes following infection with Mycobacterium tuberculosis are still not defined. We used specific pharmacologic inhibitors to identify the signalling molecules which lead interleukin (IL)-8 and MCP-1 monocytes response M. infection. Inhibition of extracellular signal-regulated (ERK) or p38 mitogen-activated protein kinase PD98059 SB203580 respectively, significantly affected production. However, only presence both completely blocked release. A down-regulation secretion was found (PK)C phospholipase C. Moreover, depended on transcription activation via nuclear factor-kappa B (NF-kappaB), as demonstrated treatment actinomycin D caffeic acid phenethyl ester. In addition, PKA phosphoinoside 3-kinase (PI-3k)/p70 ribosomal S6 cascade required have maximal but IL-8 conclusion, this study provides evidence that multiple signal transduction pathways -induced monocytes. for first time report indicates some able dissociate from secretion. Differences regulatory can potentially be exploited therapeutically.