Effects of Pim-1 inhibitor on mouse model of inflammatory bowel disease induced by TNBS
10.11817/j.issn.1672-7347.2018.05.004
- VernacularTitle:Pim-1抑制剂对TNBS诱导的小鼠炎症性肠病的疗效
- Author:
Rong OU
1
;
Yueming SHEN
;
Ya ZENG
;
Lingzhi ZOU
;
Na JIANG
;
Meihua XU
Author Information
1. 淮安市康复医院消化内科
- Keywords:
Pim-1 inhibitor;
steroid hormone;
immune inflammation;
2,4,6-trinitrobenzenestdfonic acid;
inflammatory bowel disease
- From:
Journal of Central South University(Medical Sciences)
2018;43(5):481-489
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of Pim-1 in the pathology of inflammatory bowel disease and the potential effect of Pim-1 inhibitor on treating such disease.Methods:Forty-five BALB/c mice were randomly divided into 5 groups (n=9):A normal control group,a inflammatory bowel disease group,two different dose of Pim-1 inhibitor treatment groups,and steroidhormone treatment group.The model of inflammatory bowel disease was induced by intracolonic administration of 2,4,6-trinitrobenzenestdfonic acid (TNBS) and ethanol mixture.Mice were treated with Pim-1 inhibitor [intraperitoneal inject,5 or 10 mg/(kg.d)] for 5 days and prednisone (intragastric administration,0.1 mg/d) for 5 days.The DAI,colon length,gross score and pathological grade were evaluated.The expressions ofT cell master transcription factors T-box expressed in T cells (T-bet),GATA binding protein 3 (GATA-3),RA orphan receptorγ (RORyt)and forkhead box P3 (Foxp3) were measured by Real-time PCR and Western blot,respectively.Results:Pim-1 inhibitor and prednisone showed therapeutic effect on acute TNBS colitis in vivo.GATA3 and RORγt were significantly up-regulated in acute TNBS colitis (P＜0.05).In contrast,the expression of Foxp3 was suppressed in the inflammatory bowel disease group,whereas it did not cause any significant change in T-bet expression (P＞0.05).Administration of Pim-1 inhibitor and prednisone resulted in suppression of GATA3,RORγt expression,and the increase of Foxp3 expression (P＜0.05).Administration of Pim-1 inhibitor and prednisone resulted in inhibition of T-bet mRNA expression (P＜0.05),but only prednisone could inhibit T-bet protein expression (P＞0.05).Conclusion:Pim-1 inhibitor significantly suppresses Th2-and Th17-type immune responses.Furthermore,Pim-1 inhibitor could induce T-cell differentiation towards a Treg phenotype.Pim-1 inhibitor has therapeutic effect on acute TNBS colitis.
