Knockdown of fatty acid binding protein 4 exacerbates Bacillus Calmette-Guerin infection-induced RAW264.7 cell apoptosis via the endoplasmic reticulum stress pathway.

Abstract

Mycobacterial infection can induce alveolar macrophage apoptosis, which plays a vital role in the pathogenesis of tuberculosis. Accumulating evidence has demonstrated that fatty acid oxidation is involved in apoptosis during various pathological processes, including bacterial infection. However, whether fatty acid oxidation regulates mycobacterial infection-induced macrophage apoptosis remains unclear. Hence, the present study aimed to investigate the role of fatty acid binding protein 4 (FABP4) which is a carrier protein for fatty acids, in regulating apoptosis in RAW264.7 cells infected with Bacillus Calmette-Guerin (BCG). In our study, the impact of BCG infection on apoptosis and fatty acid oxidation in RAW264.7 cells was examined. Notably, we found that FABP4 was overexpressed during this process. Furthermore, small interfering RNAs targeting FABP4 were used to investigate the role of FABP4 in regulating apoptosis and fatty acid oxidation in BCG-infected RAW264.7 cells. The results indicated that mycobacterial infection promoted apoptosis and enhanced fatty acid oxidation in RAW264.7 cells. Moreover, FABP4 knockdown exacerbated BCG-induced apoptosis and upregulated the expression of p-PERK, p-eIF2α and chop, which are endoplasmic reticulum (ER) stress markers. In addition, FABP4 knockdown promoted fatty acid oxidation and ROS production, which result in the activation of ER stress. Our data suggested that FABP4 knockdown exacerbated BCG-induced apoptosis in RAW264.7 cells via the ER stress pathway.