Excess fatty acids induce pancreatic acinar cell pyroptosis through macrophage M1 polarization

BMC Gastroenterology

Wenwen Xia¹  Wei Chen¹  Yan Zhao¹  Zhaomin Lu²  Jianjun Zhou³ 

[1] Department of Gastroenterology, Shanghai Tenth People’s Hospital of Tongji University, 301 Middle Yanchang Road, 200072, Jing’an, Shanghai, China;Department of Gastroenterology, Zhangjiagang Second People’s Hospital, 215633, Zhangjiagang, Jiangsu, China;Research Center for Translational Medicine, Cancer Stem Cell Institute, East Hospital, Tongji University School of Medicine, 150 Jimo Road, 200135, Pudong, Shanghai, China;

关键词: Free fatty acid;    Cathepsin S;    Acinar cell;    Pyroptosis;    Hyperlipidemia;    Pancreatitis;   

DOI  :  10.1186/s12876-022-02146-8

来源: Springer

【 摘 要 】

Free fatty acid derived from hyperlipidemia contributes to the development of inflammation in the pancreas. Here we explore the molecular mechanisms of fatty acid-induced pancreatitis through cellular experiments and the construction of a mouse model of hyperlipidemic pancreatitis. We found that palmitic acid stimulation leads to M1 polarization of macrophage, which secretes cathepsin S via exosomes to pancreatic acinar cells and leads to activation of the caspase1-mediated classical pyrolysis pathway, resulting in inflammation and pancreatic tissue damage. In vivo experiments have also demonstrated that the high levels of fatty acids induced by hyperlipidaemia exacerbate the development of pancreatitis, and that cathepsin S inhibitors significantly alleviate hyperlipidemic pancreatitis. Therefore, cathepsin S may be a new target for the clinical treatment of hyperlipidemic pancreatitis.

【 授权许可】

CC BY