GPR84-mediated inhibition of PANopotsis of cardiomyocyte alleviates sepsis-induced myocardial dysfunction

Background Sepsis-induced myocardial dysfunction (SIMD) is the main complications of sepsis. GPR84 exerts protective function various heart diseases. This study aimed to investigate the role of GPR84 in SIMD. Methods Lipopolysaccharide (LPS) injection was used to establish mouse sepsis model. Cytokine release was detected using ELISA. Gene expression was detected using RT-qPCR, western blot, and immunofluorescence. Mitochondrial respiration was detected using OCR assay. Mitochondrial ROS was detected using DHE and mitoSOX staining. Mitochondrial membrane potential was detected using TMRM staining. Cell viability was detected using CCK-8 assay. Cell death was detected using TUNEL. Results We found that GPR84 expression was downregulated in SIMD. However, overexpressed GPR84 restored mitochondrial functions as well as suppressed the PANoptosis of cardiomyocytes. Mechanically, GPR84 inhibited the expression of ARRB2. However, overexpressed ARRB2 impaired mitochondrial functions and promoted the PANoptosis of cardiomyocytes. Conclusions In summary, GPR84 maintains mitochondrial functions suppresses the PANoptosis of cardiomyocytes via downregulating ARRB2. Therefore, targeting GPR84 may be a promising strategy for SIMD.