Inhibition of the p38 pathway upregulates macrophage JNK and ERK activities, and the ERK, JNK, and p38 MAP kinase pathways are reprogrammed during differentiation of the murine myeloid M1 cell line.
Mitogen-activated protein (MAP) kinases have been implicated as important mediators of the inflammatory response. Here we report that c-Jun NH(2)-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAP kinase activities are reprogrammed during the IL-6 induced macrophage-like differentiation of the murine myeloid M1 cell line. Moreover, p38 inhibition upregulates JNK and ERK activity in M1 cells and in thioglycollate-elicited peritoneal exudate macrophages. IL-6-induced M1 differentiation also induces expression of the anti-inflammatory cytokine IL-10, and p38 inhibition potentiates this increase in IL-10 expression in an ERK-dependent manner. Thus, we speculate that during inflammatory conditions in vivo macrophage p38 may regulate JNK and ERK activity and inhibit IL-10 expression. These data highlight the importance of p38 in the molecular mechanisms of macrophage function.
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
J Perry
JP
Hall
Roger J
RJ
Davis
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D022423:Myeloid Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases