[HTML][HTML] LPS-induced chemokine expression in both MyD88-dependent and-independent manners is regulated by Cot/Tpl2-ERK axis in macrophages

K Bandow, J Kusuyama, M Shamoto, K Kakimoto… - FEBS letters, 2012 - Elsevier
K Bandow, J Kusuyama, M Shamoto, K Kakimoto, T Ohnishi, T Matsuguchi
FEBS letters, 2012Elsevier
LPS signaling is mediated through MyD88-dependent and-independent pathways,
activating NF-κB, MAP kinases and IRF3. Cot/Tpl2 is an essential upstream kinase in LPS-
mediated activation of ERKs. Here we explore the roles of MyD88 and Cot/Tpl2 in LPS-
induced chemokine expression by studying myd88−/− and cot/tpl2−/− macrophages. Among
the nine LPS-responsive chemokines examined, mRNA induction of ccl5, cxcl10, and cxcl13
is mediated through the MyD88-independent pathway. Notably, Cot/Tpl2-ERK signaling axis …
LPS signaling is mediated through MyD88-dependent and -independent pathways, activating NF-κB, MAP kinases and IRF3. Cot/Tpl2 is an essential upstream kinase in LPS-mediated activation of ERKs. Here we explore the roles of MyD88 and Cot/Tpl2 in LPS-induced chemokine expression by studying myd88−/− and cot/tpl2−/− macrophages. Among the nine LPS-responsive chemokines examined, mRNA induction of ccl5, cxcl10, and cxcl13 is mediated through the MyD88-independent pathway. Notably, Cot/Tpl2-ERK signaling axis exerts negative effects on the expression of these three chemokines. In contrast, LPS-induced gene expression of ccl2, ccl7, cxcl2, cxcl3, ccl8, and cxcl9 is mediated in the MyD88-dependent manner. The Cot/Tpl2-ERK axis promotes the expression of the first four and inhibits the expression of the latter two. Thus, LPS induces expression of multiple chemokines through various signaling pathways in macrophages.
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