Acute pancreatitis (AP) is an acute abdominal disease characterised by inflammation of the pancreas. Acute severe upper abdominal pain is the leading symptom and primary reason for emergence hospital admission of AP patients. Nowadays, more and more research has focused on the cross-talk between the exocrine pancreas and pancreatic projecting neurons (neurogenic inflammation) for pain in AP. Elucidating the molecular mechanisms of neurogenic inflammation for pain in AP will provide insights into targeted analgesics development in this setting.
ObjectiveTo investigate the effects of generic interleukin (IL)-17A gene knockout (IL-17AKO) on pancreatic and intestinal barrier on acute pancreatitis (AP) in mice. MethodsIL-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. ResultsIn 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. ConclusionsIL-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.