Shen Yueming, Xie Yuanhong, Zhao Yan, Long Yan, Li Lingqian, Zeng Ya
Department of Digestive Diseases, Changsha Central Hospital, No. 163, Shaoshan Nanlu, Changsha 410004, China.
Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, No. 145, Shandong Zhonglu, Shanghai 200001, China.
Clin Res Hepatol Gastroenterol. 2018 Sep;42(4):382-386. doi: 10.1016/j.clinre.2018.01.002. Epub 2018 Mar 16.
Pim-1 kinase has been implicated in inflammatory bowel disease (IBD). This study aimed to evaluate the application of Pim-1 inhibitor (PIM-Inh) for the treatment of IBD. Mouse model of IBD was established by the treatment with trinitrobenzene sulphonic acid (TNBS). The results showed that disease activity index score was significantly decreased, colon length was significantly increased while Wallace score and pathological score were significantly decreased after PIM-Inh treatment compared to TNBS model group. In addition, GATA3 and ROR-γt mRNA and protein levels significantly increased but Foxp3 mRNA and protein levels significantly decreased in mice with TNBS treatment compared to mice without TNBS treatment. Administration of PIM-Inh caused significant decreases in GATA3, T-bet and ROR-γt mRNA and protein levels as well as significant increases in FOXP3 mRNA and protein levels. In conclusion, our data suggest that Pim-1 kinase inhibitor could attenuate IBD by promoting T-cell differentiation into Foxp3 regulatory T-cells and is a promising agent for IBD therapy.
Pim-1激酶与炎症性肠病(IBD)有关。本研究旨在评估Pim-1抑制剂(PIM-Inh)在IBD治疗中的应用。通过三硝基苯磺酸(TNBS)处理建立IBD小鼠模型。结果显示,与TNBS模型组相比,PIM-Inh治疗后疾病活动指数评分显著降低,结肠长度显著增加,而华莱士评分和病理评分显著降低。此外,与未接受TNBS处理的小鼠相比,接受TNBS处理的小鼠中GATA3和ROR-γt mRNA及蛋白水平显著升高,但Foxp3 mRNA和蛋白水平显著降低。给予PIM-Inh导致GATA3、T-bet和ROR-γt mRNA及蛋白水平显著降低,同时FOXP3 mRNA和蛋白水平显著升高。总之,我们的数据表明,Pim-1激酶抑制剂可通过促进T细胞分化为Foxp3调节性T细胞来减轻IBD,是一种有前途的IBD治疗药物。