Silencing of SPI1/OLAH Axis Inhibits Pancreatic Acinar Cell Oxidative Stress, Inflammation and Apoptosis to Alleviate Hyperlipidemic Acute Pancreatitis

BACKGROUND: Oleoyl-ACP hydrolase (OLAH), a fatty acid metabolism-related gene, is abnormally expressed in many diseases. Using the GEO database, we found that OLAH was highly expressed in acute pancreatitis (AP) patients. However, whether it mediates hyperlipidemic AP (HAP) progression remains unclear. MATERIALS AND METHODS: Mouse pancreatic acinar cells (MPC-83) were treated with palmitic acid (PA) and cerulein (CER) to mimic HAP cell models, and HAP mice models were constructed by injecting with P-407 and CER. The mRNA and protein levels of OLAH and Salmonella pathogenicity island 1 (SPI1) were determined by qRT-PCR and western blot. The oxidative stress and inflammation in MPC-83 cells and the pancreatic tissues of HAP mice models were assessed by measuring the levels of MDA, SOD, ROS, IL-1β, TNF-α and IL-6. Cell apoptosis was examined using flow cytometry. The interaction between SPI1 and OLAH promoter was evaluated using ChIP assay and dual-luciferase reporter assay. RESULTS: OLAH was upregulated in PA+CER-induced MPC-83 cells, and its silencing suppressed pancreatic acinar cell oxidative stress, inflammation and apoptosis. Transcription factor SPI1 bound to OLAH promoter region to enhance its expression. SPI1 knockdown inhibited PA+CER-induced MPC-83 cell oxidative stress, inflammation and apoptosis, as well as alleviated HAP process in mice models, while these effects were reversed by OLAH overexpression. CONCLUSION: SPI1-mediated transcriptional activation of OLAH promoted pancreatic acinar cell oxidative stress, inflammation and apoptosis to accelerate HAP progression.