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

Abstract

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.