Effects of generic IL-17A gene knockout on the severity of acute pancreatitis in mice
Objective To investigate the effects of generic interleukin(IL)-17A gene knockout(IL-17AKO)on pancreatic and intestinal barrier on acute pancreatitis(AP)in mice.Methods IL-17AKO mice and their wild type(WT)littermates were employed to induce AP using cerulein(CER)and sodium taurocholate(NaTC).In the CER-AP experiment,mice were randomly divided into three groups:WT control group,WT model group,and IL-17AKO model group(n=5).Mice in the model group were intraperitoneally injected with CER[50 μg/(kg·h),7 injections],and control group received intraperitoneal injection the same amount of 0.9％NaCl.The mice were sacrificed at 12 hours after the first injection of CER.The levels of serum amylase,lipase and IL-6 were detected,and the pancreas was stained with hematoxylin-eosin(HE).In the NaTC-AP experiment,WT mice were randomly divided into sham group(n=3)and operation model group(n=6).Similarly,IL-17AKO mice were also randomly allocated to sham group(n=3)and operation model group(n=6).The mice in the sham group underwent a surgical procedure on the abdomen only,whereas in the model group,50 μL 3.5％NaTC dissolved in saline solution was pumped into the pancreatobiliary duct.Serum amylase,lipase,and IL-6 levels were detected.Pancreas was stained with HE,and intestine was stained with Alcian blue-periodic acid-Schiff,Dolichos Biflorus Agglutinin and bacteria fluorescence in situ hybridization.Results In the CER-AP experiment,there were no significant differences in serum amylase,lipase,IL-6,and pathological changes including edema,inflammation,necrosis,and total pathological score of the pancreas between IL-17AKO and WT mice(P＞0.05).In the NaTC-AP experiment,compared to the WT model group,IL-17AKO did not significantly impact serum amylase,lipase,and pancreatic pathological changes(P＞0.05).However,it did lead to an increased level of IL-6(P＜0.05),and showed no significant protective effect on intestinal injury in NaTC-AP.Compared to WT mice of sham group,IL-17AKO mice of sham group exhibited decreased expressions of glycosylated mucin in ileum and colon,disordered mucus layer structure,and increased bacterial invasion.Conclusions IL-17AKO has no significant protective effect on pancreatic and intestinal barrier damage in AP mice.Furthermore,it was discovered that prior to modeling,IL-17AKO mice exhibited higher bacterial invasion,intestinal barrier disruption,and a systemic inflammatory response.These findings imply that IL-17A plays a crucial role in immune responses and the maintenance of physiological intestinal barrier function in mice.
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