IL-17 stimulates the expression of CCL2 in cardiac myocytes via Act1/TRAF6/p38MAPK-dependent AP-1 activation.

IL-17 participates in the development of many autoimmune diseases by promoting the expression of some chemokines. Chemokine C-C motif ligand 2 (CCL2) is an important factor at the infiltration of mononuclear cells in the myocardial tissue of viral myocarditis (VMC). It was found that IL-17 could aggravate myocardial injury by upregulating CCL2. But the underlying mechanism involved in CCL2 secretion induced by IL-17 in cardiac myocytes remains unclear. This study investigated the role of transcription factor AP-1 in IL-17 induced CCL2 expression. The results showed that IL-17 mediated the activation of Act1, TRAF6, p38MAPK and c-Jun/AP-1 not Wnt or PI3K signalling pathway to upregulate CCL2 expression in cardiac myocytes. After blocking Act1/TRAF6/p38MAPK cascade and interfering AP-1 with Curcumin or c-Jun siRNA, CCL2 expression induced by IL-17 was significantly attenuated at both mRNA and protein levels. Furthermore, the phosphorylation of c-Jun was suppressed when cardiac myocytes were treated with Act1 siRNA, TRAF6 siRNA, SB203580 (p38MAPK inhibitor) or SP600125 (JNK inhibitor) in cardiac myocytes. In conclusion, IL-17 could stimulate the expression of CCL2 in cardiac myocytes via Act1/TRAF6/p38MAPK-dependent AP-1 activation, which may provide a new target for the diagnosis and treatment of VMC.