Novel activity of an anti-inflammatory cytokine: IL-10 prevents TNFalpha-induced resistance to IGF-I in myoblasts.
IL-10 is an anti-inflammatory cytokine that suppresses synthesis of proinflammatory cytokines and their receptors. Here we tested the possibility that TNFalpha-induced hormone resistance in myoblasts might be overcome by IL-10. We found that IL-10 restores myogenesis by suppressing the ability of exogenous TNFalpha to inhibit IGF-I-induced myogenin. This protection occurs without decreasing global activity of TNF receptors since IL-10 does not impair TNFalpha-induced IL-6 synthesis or ERK1/2 phosphorylation. Instead, IL-10 acts to prevent TNFalpha-induced phosphorylation of JNK. These findings demonstrate that IL-10 serves a previously unrecognized protective role in muscle progenitors by overcoming TNFalpha-induced resistance to IGF-I.
Strle
Klemen
K
Laboratories of Integrative Immunophysiology, College of Medicine, University of Illinois, Urbana, IL 61801, United States.
McCusker
Robert H
RH
Tran
Lynn
L
King
Alexandra
A
Johnson
Rodney W
RW
Freund
Gregory G
GG
Dantzer
Robert
R
Kelley
Keith W
KW
D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects*; D018008:Myogenin / Q000378:metabolism
D007155:Immunologic Factors; D016898:Interferon-alpha; D015850:Interleukin-6; D018008:Myogenin; D016753:Interleukin-10; D007334:Insulin-Like Growth Factor I; D020928:Mitogen-Activated Protein Kinases