Author/Editor		Strle, Klemen; McCusker, Robert H; Johnson, Rodney W; Zunich, Samantha M; Dantzer, Robert; Kelley, Keith W
Title		Prototypical anti-inflammatory cytokine IL-10 prevents loss of IGF-I-induced myogenin protein expression caused by IL-1beta
Type		članek
Source		Am J Physiol Endocrinol Metab
Vol. and No.		Letnik 294, št. 4
Publication year		2008
Volume		str. E709-18
Language		eng
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-1beta 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-1beta-induced synthesis of IL-6 or the ability of IL-1beta 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-1beta activation of the JNK kinase pathway. IL-10 blocks IL-1beta-induced phosphorylation of JNK, but not ERK1/2 or p38, indicating that only the JNK component of the IL-1beta-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-1beta. Collectively, these data demonstrate that IL-10 acts in a novel, nonclassical, protective manner in nonhematopoietic cells to inhibit the IL-1beta receptor-induced JNK kinase pathway, resulting in prevention of IGF-I resistance.
Descriptors		INTERLEUKIN-10 INSULIN-LIKE GROWTH FACTOR I INTERLEUKIN-1 MYOGENIN INTERLEUKIN-6 MYOSIN HEAVY CHAINS RECOMBINANT PROTEINS ANTIBODIES, MONOCLONAL MUSCLE, SKELETAL CELLS, CULTURED