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The Immunomodulatory Effects and Mechanisms of Tim-3 Action in the Early Stage of Mice with Severe Acute Pancreatitis | ||
Iranian Journal of Immunology | ||
مقاله 5، دوره 17، شماره 1، خرداد 2020، صفحه 52-63 اصل مقاله (853.28 K) | ||
نوع مقاله: Original Article | ||
شناسه دیجیتال (DOI): 10.22034/iji.2020.80294 | ||
نویسندگان | ||
Min Lin1؛ Jin Huang1؛ Wei-Chang Chen2؛ Zhi-Ning Fan3؛ Xihu Qin* 4 | ||
1Department of Gastroenterology, The Affiliated Changzhou No.2 People’s Hospital with Nanjing Medical University, Changzhou, China | ||
2Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China | ||
3Digestive Endoscopy Department, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China | ||
4Department of General Surgery, The Affiliated Changzhou No.2 People’s Hospital with Nanjing Medical University, Changzhou, China | ||
چکیده | ||
Background: Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well. Objective: To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice. Methods: Male BALB/c mice were randomly divided into sham injection group, severe acute pancreatitis group, and anti-Tim-3 treated group. Histopathological scores of the pancreas were calculated, pancreatic myeloperoxidase (MPO) activity was assessed. The concentrations of serum IL-6, IL-10, and TNF-α were evaluated by ELISA kits. Quantitative RT-PCR was performed to detect the transcript amounts of Tim-3, IL-6, IL-10, TNF-α, and TLR4 in peritoneal macrophages. The levels of peritoneal macrophages Tim-3, TLR4, MyD88, and NF-kB p65 were measured by western blot analysis. Results: The pathological scores of the anti-Tim-3 treated group (11.5 ± 1.3) significantly increased compared with the sham (1.3 ± 0.5) and SAP groups (6.9 ± 1.0). Furthermore, the downregulation of Tim-3 significantly aggravated mouse pancreatic tissue damage. It was further shown that Tim-3 negatively regulated the production of pro-inflammatory cytokines, IL-6 and TNF-α, as well as anti-inflammatory cytokine IL-10. Of note, the negative regulation of inflammatory cytokines by Tim-3 was mediated by the activation of TLR4/MyD88 NF-kB signaling pathway. Conclusion: Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response. | ||
کلیدواژهها | ||
Acute Pancreatitis؛ Peritoneal Macrophage؛ Tim-3 | ||
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