Lin Min, Huang Jin, Chen Wei-Chang, Fan Zhi-Ning, Qin Xihu
Department of Gastroenterology, The Affiliated Changzhou No.2 People's Hospital with Nanjing Medical University, Changzhou, China.
Iran J Immunol. 2020 Mar;17(1):52-63. doi: 10.22034/iji.2020.80294.
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.
To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice.
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 method. Quantitative RT-PCR was performed to detect the transcripts 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.
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.
Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response.
Tim-3被认为是炎症免疫治疗的理想靶点，但Tim-3在急性胰腺炎（AP）中是否也发挥重要作用尚不清楚。
明确Tim-3在小鼠重症急性胰腺炎早期的免疫调节作用及机制。
将雄性BALB/c小鼠随机分为假注射组、重症急性胰腺炎组和抗Tim-3治疗组。计算胰腺组织病理学评分，评估胰腺髓过氧化物酶（MPO）活性。采用ELISA法检测血清白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和肿瘤坏死因子-α（TNF-α）浓度。运用定量RT-PCR检测腹膜巨噬细胞中Tim-3、IL-6、IL-10、TNF-α和Toll样受体4（TLR4）的转录本。通过蛋白质印迹分析测定腹膜巨噬细胞中Tim-3、TLR4、髓样分化因子88（MyD88）和核因子-κB p65的水平。
抗Tim-3治疗组的病理评分（11.5±1.3）与假手术组（1.3±0.5）和重症急性胰腺炎组（6.9±1.0）相比显著升高。此外，Tim-3的下调显著加重了小鼠胰腺组织损伤。进一步研究表明，Tim-3对促炎细胞因子IL-6和TNF-α以及抗炎细胞因子IL-10的产生具有负调控作用。值得注意的是，Tim-3对炎性细胞因子的负调控是通过激活TLR4/MyD88核因子-κB信号通路介导的。
我们的研究表明，Tim-3可能通过调节炎症反应在急性胰腺炎的发展中发挥重要作用。
