The Immunomodulatory Effects and Mechanisms of Tim-3 Action in the Early Stage of Mice with Severe Acute Pancreatitis |
| |
| Authors: | Min LinJin HuangWei-Chang ChenZhi-Ning FanXihu Qin |
| |
| Affiliation: | 1Department of Gastroenterology, The Affiliated Changzhou No.2 People’s Hospital with Nanjing Medical University, Changzhou, China2Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China3Digestive Endoscopy Department, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China4Department of General Surgery, The Affiliated Changzhou No.2 People’s Hospital with Nanjing Medical University, Changzhou, China |
| |
| Abstract: | 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. |
| |
| Keywords: | Acute Pancreatitis Peritoneal Macrophage Tim-3 |
|
| 点击此处可从《Iranian journal of immunology : IJI》浏览原始摘要信息 |
|
点击此处可从《Iranian journal of immunology : IJI》下载免费的PDF全文 |
|
