Impacts of shikonin on lipopolysaccharide-induced inflammation and apoptosis of pancreatic acinar cells by regulating SOCS1/JAK2/STAT3 signaling pathway

Objective: To explore the impacts of shikonin on lipopolysaccharide (LPS)-induced inflammation and apoptosis of pancreatic acinar cells by regulating SOCS1/JAK2/STAT3 signaling pathway. Methods: Rat pancreatic acinar cells AR42J were cultured in vitro,the cells were transfected with si-NC and si-SOCS1,then treated with LPS and/or high-dose shikonin.The untransfected cells were divided into Control group,LPS group,and low/medium/high-dose shikonin group (L/M/H-shikonin group) which were treated with LPS except Control,and the transfected cells were divided into si-NC group,si-SOCS1 group,H-shikonin+si-NC group and H-shikonin+si-SOCS1 group which were all treated with LPS.The expression of inflammatory factors interleukin 1β (IL-1β),tumor necrosis factor α (TNF-α) was detected by ELISA,the cell viability was determined by CCK-8 method,the apoptosis was detected by flow cytometry,and the expression of SOCS1/JAK2/STAT3 signaling pathway-related proteins were analyzed by Western blotting. Results: Compared with the Control group,the levels of IL-1β,TNF-α and apoptosis rate in AR42J cells in the LPS group increased,while the OD450 value decreased (P<0.05).Compared with the LPS group,the levels of IL-1β,TNF-α and apoptosis rate in AR42J cells in the L/M/H-shikonin group decreased,while the OD450 value increased,and which in the H-shikonin group decreased or increased more (P<0.05).Compared with the control group,the SOCS1 protein level in AR42J cells in the LPS group decreased,while the p-JAK2 and p-STAT3 protein level increased (P<0.05).Compared with the LPS group,the SOCS1 protein level in AR42J cells in the H-shikonin group increased,while the p-JAK2 and p-STAT3 proteins decreased (P<0.05);the SOCS1 protein level in AR42J cells in the si-SOCS1group decreased,while the p-JAK2 and p-STAT3 protein level increased (P<0.05).Compared with the H-shikonin group,the SOCS1 protein level in AR42J cells in the H-shikonin+si-SOCS1 group decreased,while the p-JAK2 and p-STAT3 protein level increased (P<0.05). Conclusions: Shikonin can inhibit the inflammatory response and apoptosis of AR42J cells induced by LPS,and enhance cell viability,which may be achieved by regulating the SOCS1/JAK2/STAT3 signaling pathway.