Micrococci and peptidoglycan activate TLR2 -> MyD88 -> IRAK -> TRAF -> NIK-> IKK -> NF-kappa B signal transduction pathway that induces transcription of interleukin-8

This study was done to elucidate the signal transduction pathway of interle ukin-8 (IL-8) induction by grampositive bacteria. Bacteria (micrococci) and peptidoglycan (PGN) induced transcription of IL-8 in HEK293 cells expressi ng Toll-like receptor 2 (TLR2) and CD14 but not in those expressing TLR1 or TLR4. A mutation within the NF-kappaB site in the IL-8 promoter abrogated transcriptional induction of IL-8 by the two stimulants. Dominant negative myeloid differentiation protein (MyD88), IL-1 receptor-associated kinase (I RAK), NF kappaB-inducing kinase (NIK), and I kappaB kinase (IKK) mutant for ms completely inhibited micrococcus- and PGN-induced activation of NF-kappa B and expression of the gene for IL-8. Induction of NF-kappaB was partially inhibited by dominant negative tumor necrosis factor receptor-associated k inase 6 (TRAF6) but not TRAF2, whereas induction of IL-8 gene was partially inhibited by both TRAF6 and TRAF2, These data indicate that micrococci and PGN induce TLR2-dependent activation of the gene for IL-8 and that this ac tivation requires MyD88, IRAK, NIK, IKK, and NF-kappaB and may also utilize TRAF6 and, to a lesser extent, TRAF2.