AbstractBackgroundAcute pancreatitis (AP) is an inflammatory process unexpectedly occurring in the pancreas, imposing a substantial burden on healthcare systems. Herein, we aimed to clarify the mechanism of action of phospholipase D2 (PLD2) in cerulein‐treated AR42J cells, affording valuable insights into the treatment of AP.MethodsThe levels of PLD2, miR‐5132‐5p, inflammatory factors (interleukin [IL]−10, IL‐6, and tumor necrosis factor‐α), caspase‐3 activity, and apoptosis‐related proteins (Bax and Bcl‐2) in cerulein‐treated AR42J cells were detected using reverse transcription‐quantitative polymerase chain, caspase‐3 activity, and Western blot analysis. Protein levels of nuclear Factor erythroid 2‐Related Factor 2 (Nrf2) and nuclear factor‐k‐gene binding (NF‐κB) were detected by Western blot analysis. TargetScan predicted upstream microRNAs (miRNAs) of PLD2, and the interaction between miR‐5132‐5p and PLD2 was verified using a luciferase assay.ResultsIn cerulein‐treated AR42J cells, PLD2 levels were downregulated, while miR‐5132‐5p expression was upregulated. Overexpression of PLD2 attenuated the cerulein‐mediated facilitatory effect on inflammation and apoptosis in AR42J cells by regulating the Nrf2/NFκB pathway. Luciferase reporter analysis revealed that miR‐5132‐5p targeted PLD2, and miR‐5132‐5p negatively regulated PLD2. Upregulation of miR‐5132‐5p expression exacerbated inflammation and apoptosis and reversed the protective effect of PLD2 overexpression on AP.ConclusionPLD2 targeted by miR‐5132‐5p can attenuate cerulein‐induced AP in AR42J cells via the Nrf2/NFκB pathway, providing therapeutic targets for patients with AP.