Prototypical anti-inflammatory cytokine IL-10 prevents loss of IGF-I-induced myogenin protein expression caused by IL-1beta
| Autor: | Robert H. McCusker, Keith W. Kelley, Robert Dantzer, Rodney W. Johnson, Klemen Strle, Samantha M. Zunich |
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| Rok vydání: | 2008 |
| Předmět: |
MAPK/ERK pathway
Physiology MAP Kinase Signaling System Endocrinology Diabetes and Metabolism medicine.medical_treatment Interleukin-1beta Inflammation Biology Article Myoblasts Mice Physiology (medical) Gene expression medicine Animals Drug Interactions Insulin-Like Growth Factor I Phosphorylation Muscle Skeletal Myogenin Cells Cultured Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Dose-Response Relationship Drug JNK Mitogen-Activated Protein Kinases Cell Differentiation Pathophysiology Interleukin-10 Interleukin 10 Cytokine Mitogen-activated protein kinase Immunology Cancer research biology.protein medicine.symptom |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 294(4) |
| ISSN: | 0193-1849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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