The LIM-only protein FHL2 regulates interleukin-6 expression through p38 MAPK mediated NF-κB pathway in muscle cells.
Interleukin 6 (IL-6) is pleiotropic cytokine playing an important role in inflammatory response. Other than classical immune tissues, IL-6 is also produced in muscle cells under specific conditions. Four-and-a-half LIM-only protein 2 (FHL2) is preferentially expressed in skeletal and cardiac muscle cells compared to other tissues indicating it has an important role in skeletal muscle and cardiovascular system. In this report, the regulation of IL-6 by FHL2 in muscle cells was investigated. We demonstrated that FHL2 overexpression increased IL-6 mRNA level and its protein secretion in skeletal myoblasts. In contrast, the IL-6 secretion was significantly decreased after FHL2-knockdown by siRNA in response to TNFα stimulation. We further showed that FHL2-mediated induction of IL-6 was regulated by the activation of IL-6 promoter through stimulating NF-κB and p38 MAPK signaling pathway. Our results further illustrated the molecular mechanisms of IL-6 production, which provides new insights in the roles of FHL2 in post-injury inflammation or cytoprotection of muscle cells.
Department of Clinical Oncology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong Special Administrative Region, China.
Chi-Hang
CH
Wong
Grace Wing-Yan
GW
Mak
Man-Shan
MS
Li
Stephen Kwok-Wing
SK
Tsui
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D032342:Muscle Cells / Q000201:enzymology* / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C491382:Fhl2 protein, mouse; D020672:I-kappa B Proteins; D015850:Interleukin-6; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors; D008156:Luciferases; D048051:p38 Mitogen-Activated Protein Kinases