IFITM3 mediates inflammation induced myocardial injury through JAK2/STAT3 signaling pathway

Myocarditis is an inflammation of the heart muscle often associated with viral infections and can lead to dilated cardiomyopathy. Interferon-induced transmembrane protein 3 (IFITM3) is a small endosomal membrane protein with anti-viral activity against multiple viruses and is also implicated in non-infectious diseases such as cancer and Alzheimer's Disease. Since the IFITM3 proteins are expressed both in T cells and in cardiomyocytes, it is reasonable to hypothesize that these molecules could affect myocarditis either through their effect on the autoimmune response or through direct modulation of cardiomyocyte damage. The aim of this study was to investigate the role of IFITM3 in experimental autoimmune myocarditis (EAM)-mediated myocardial injury. Immunization of rats with cardiac myosin results in substantial cardiac inflammation and is associated with increased expression of IFITM3 after 21 days. In vivo IFITM3 shRNA knockdown using the lentivirus transfection method reduced cardiac injury while restoring IFITM3 expression reversed the protective effect of IFITM3 RNA interference. To determine the direct impact of IFITM3, the rat ventricular cell line, H9c2, was treated with palmitic acid which causes apoptosis in these cells. Suppressing IFITM3 expression protects H9c2 cells while overexpressing IFITM3 enhances cell injury. JAK inhibitors reduced IFITM3-mediated myocardial cell injury. In conclusion, IFITM3 may mediate myocardial injury in EAM rats and palmitic acid-induced damage to H9c2 cells through the JAK2/STAT3 pathway.