TY - JOUR
T1 - LPS-induced chemokine expression in both MyD88-dependent and -independent manners is regulated by Cot/Tpl2-ERK axis in macrophages
AU - Bandow, Kenjiro
AU - Kusuyama, Joji
AU - Shamoto, Mitsuo
AU - Kakimoto, Kyoko
AU - Ohnishi, Tomokazu
AU - Matsuguchi, Tetsuya
N1 - Funding Information:
This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant 23592739 to K.B., Grant 23592740 to T.O. and Grant 23592741 to T.M.).
PY - 2012/5/21
Y1 - 2012/5/21
N2 - 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.
AB - 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.
KW - Chemokine
KW - Cot/Tpl2
KW - ERK
KW - LPS
KW - Macrophage
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U2 - 10.1016/j.febslet.2012.04.018
DO - 10.1016/j.febslet.2012.04.018
M3 - Article
C2 - 22673523
AN - SCOPUS:84861202872
VL - 586
SP - 1540
EP - 1546
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 10
ER -