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

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• 作者：Kenjiro Bandow ; Joji Kusuyama ; Mitsuo Shamoto ; Kyoko Kakimoto ; Tomokazu Ohnishi ; Tetsuya Matsuguchi ; ^{tmatsugu@dent.kagoshima-u.ac.jp}
• 关键词：LPS ; lipopolysaccharide ; Myd88 ; myeloid differentiation factor 88 ; NF-魏B ; nuclear factor-kappa B ; MAP kinase ; mitogen-activated protein kinase ; IRF3 ; interferon regulatory factor 3 ; ERK ; extracellular signal-regulated kinase ; CCL ; chemokine CC motif liga
• 出版年：2012
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：21 May, 2012
• 卷：586
• 期：10
• 页码：1540-1546
• 文件大小：974 K

摘要

LPS signaling is mediated through MyD88-dependent and -independent pathways, activating NF-魏B, 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^{鈭?鈭?/sup> and cot/tpl2鈭?鈭?/sup> 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.}