Pim-3 Alleviates Lipopolysaccharide-stimulated AR42J Pancreatic Acinar Cell Injury Via Improving the Inflammatory Microenvironment

Acute pancreatitis (AP) is a common acute abdominal disease characterized by pancreatic aseptic inflammation, with ~20% of patients progressing to severe AP (SAP) with a high mortality rate. The aim of this study was to explore the protective effects of Pim-3 proto-oncogene, serine/threonine kinase (Pim-3) on rat pancreatic acinar AR4-2J cells damaged by lipopolysaccharide (LPS). The recombinant plasmid p-enhanced green fluorescent protein (pEGFP)-N2/Pim-3 was transiently transfected into AR42J cells and the AR42J cells were then treated with 2 µg/ml LPS. Subsequently, the proliferation of AR42J cells was detected using MTT assay. The cell cycle progression and apoptosis rate of the AR42J cells were examined using flow cytometry. AR42J cell migration was assessed using wound healing assays. Additionally, RT-semi quantitative PCR and western blot analyses were used to detect the mRNA and protein expression levels, respectively, of Pim-3, interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1 and Occludin in AR42J cells. The results revealed that proliferation of AR42J cells was significantly enhanced and cell apoptosis was markedly reduced in the pEGFP-N2/Pim-3 + LPS group. The proportion of AR42J cells in G1 phase in the pEGFP-N2/Pim-3 + LPS group was decreased, whereas the proportion of cells in the G2 and S phases was increased. The wound healing assays demonstrated that AR42J cell migration was significantly increased in the pEGFP-N2/Pim-3 + LPS group. Finally, the expression levels of IL-6, IL-1β, TNF-α and ICAM-1 were significantly decreased in the pEGFP-N2/Pim-3 + LPS group, whereas the expression of Occludin was significantly increased. The present study demonstrated that raised expression levels of Pim-3 can protect AR42J cells from LPS-induced injury by modifying the inflammatory microenvironment, suggesting that Pim-3 may be a potential target for AP or SAP therapy.