The role of PLIN2 gene in macrophages and its effect on acute pancreatitis.

Abstract

Background and objective: Acute pancreatitis (AP) is a severe inflammatory disease with limited therapeutic options. This study aimed to investigate the role of Perilipin 2 (PLIN2) in macrophage polarization and its impact on AP progression.

Methods: An AP mouse model was established using sodium taurocholate. In vitro, pancreatic acinar cells were treated with lipopolysaccharide (LPS) and caerulein (CAE) and co-cultured with RAW 264.7 macrophages. Pancreatic acinar cells were treated with lipopolysaccharide (LPS) and caerulein (CAE). Techniques included immunohistochemistry (IHC), Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays to assess macrophage polarization, lipid deposition, and cell damage.

Results: In AP, PLIN2 expression was significantly upregulated, correlating with enhanced M1 macrophage polarization and excessive lipid droplet accumulation in pancreatic tissue. Genetic knockdown of PLIN2 effectively reduced lipid deposition, suppressed pro-inflammatory M1 polarization, and promoted anti-inflammatory M2 macrophage polarization, leading to marked attenuation of pancreatic cell damage and apoptosis. Notably, these protective effects were counteracted by the overexpression of cyclic GMP-AMP synthase (cGAS), which restored lipid deposition and M1 polarization.

Conclusions: PLIN2 regulates macrophage polarization and lipid metabolism in AP, with its knockdown alleviating tissue damage by suppressing M1 polarization and promoting M2 polarization, suggesting its potential as a therapeutic target for AP management.