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.