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• W2102219247 abstract "Prolonged and excessive inflammation is implicated in resistance to the biological actions of IGF-I and contributes to the pathophysiology of neurodegenerative, metabolic, and muscle-wasting disorders. IL-10 is a critical anti-inflammatory cytokine that restrains inflammatory responses in macrophages and T cells by inhibiting cytokine and chemokine synthesis and reducing expression of their receptors. Here we demonstrate that IL-10 plays a protective role in nonhematopoietic cells by suppressing the ability of exogenous IL-1β to inhibit IGF-I-induced myogenin and myosin heavy chain expression in myoblasts. This action of IL-10 is not caused by impairment of IL-1β-induced synthesis of IL-6 or the ability of IL-1β to activate two members of the MAPK family, ERK1/2 and p38. Instead, this newly defined protective role of IL-10 occurs by specific reversal of IL-1β activation of the JNK kinase pathway. IL-10 blocks IL-1β-induced phosphorylation of JNK, but not ERK1/2 or p38, indicating that only the JNK component of the IL-1β-induced MAPK signaling pathway is targeted by IL-10. This conclusion is supported by the finding that a specific JNK inhibitor acts similarly to IL-10 to restore IGF-I-induced myogenin expression, which is suppressed by IL-1β. Collectively, these data demonstrate that IL-10 acts in a novel, nonclassical, protective manner in nonhematopoietic cells to inhibit the IL-1β receptor-induced JNK kinase pathway, resulting in prevention of IGF-I resistance." @default.
• W2102219247 created "2016-06-24" @default.
• W2102219247 creator A5005642782 @default.
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• W2102219247 creator A5078488552 @default.
• W2102219247 date "2008-04-01" @default.
• W2102219247 modified "2023-10-16" @default.
• W2102219247 title "Prototypical anti-inflammatory cytokine IL-10 prevents loss of IGF-I-induced myogenin protein expression caused by IL-1β" @default.
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• W2102219247 doi "https://doi.org/10.1152/ajpendo.00662.2007" @default.
• W2102219247 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2951888" @default.
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