LPS-induced chemokine expression in both MyD88-dependent and -independent manners is regulated by Cot/Tpl2-ERK axis in macrophages
| Autor: | Kenjiro Bandow, Tetsuya Matsuguchi, Mitsuo Shamoto, Joji Kusuyama, Tomokazu Ohnishi, Kyoko Kakimoto |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
LPS Macrophage Biophysics CCL7 Biochemistry Cell Line Mice Cot/Tpl2 Structural Biology Genetics Animals CXCL10 Extracellular Signal-Regulated MAP Kinases Molecular Biology DNA Primers Base Sequence biology Chemistry Macrophages Cell Biology Molecular biology Mice Inbred C57BL ERK CXCL2 CXCL3 Chemokine TRIF Mitogen-activated protein kinase Myeloid Differentiation Factor 88 biology.protein CXCL9 Chemokines Signal transduction |
| Zdroj: | FEBS Letters. 586:1540-1546 |
| ISSN: | 0014-5793 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text