Prototypical anti-inflammatory cytokine IL-10 prevents loss of IGF-I-induced myogenin protein expression caused by IL-1β

Klemen Strle, Robert H. McCusker, Rodney W. Johnson, Samantha M. Zunich, Robert Dantzer, Keith W. Kelley

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)E709-E718
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume294
Issue number4
DOIs
StatePublished - Apr 2008

Keywords

  • Cytokines
  • Inflammation
  • MAPK
  • Myogenin
  • Nonhematopoietic cells
  • Skeletal muscle
  • c-Jun NH-terminal kinase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Prototypical anti-inflammatory cytokine IL-10 prevents loss of IGF-I-induced myogenin protein expression caused by IL-1β'. Together they form a unique fingerprint.

Cite this