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- Title
Excess fatty acids induce pancreatic acinar cell pyroptosis through macrophage M1 polarization.
- Authors
Xia, Wenwen; Lu, Zhaomin; Chen, Wei; Zhou, Jianjun; Zhao, Yan
- Abstract
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.
- Subjects
PANCREATIC acinar cells; FATTY acids; FREE fatty acids; PYROPTOSIS; PALMITIC acid
- Publication
BMC Gastroenterology, 2022, Vol 22, Issue 1, p1
- ISSN
1471-230X
- Publication type
journal article
- DOI
10.1186/s12876-022-02146-8