PMID- 29886462 OWN - NLM STAT- MEDLINE DCOM- 20181106 LR - 20181106 IS - 1672-7347 (Print) IS - 1672-7347 (Linking) VI - 43 IP - 5 DP - 2018 May 28 TI - [Effects of Pim-1 inhibitor on mouse model of inflammatory bowel disease induced by TNBS]. PG - 481-489 LID - 10.11817/j.issn.1672-7347.2018.05.004 [doi] AB - 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 of T cell master transcription factors T-box expressed in T cells (T-bet), GATA binding protein 3 (GATA-3), RA orphan receptorgamma (RORgammat) 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 RORgammat 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, RORgammat 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. FAU - Ou, Rong AU - Ou R AD - Department of Gastroenterology, Huai'an Rehabilitation Hospital, Huai'an Jiangsu 211600, China. FAU - Shen, Yueming AU - Shen Y AD - Department of Gastroenterology, 
Changsha Central Hospital, Changsha 410004, China. FAU - Zeng, Ya AU - Zeng Y AD - Department of Gastroenterology, 
Changsha Central Hospital, Changsha 410004, China. FAU - Zou, Lingzhi AU - Zou L AD - Department of Gastroenterology, Xiangya Hospital, Central South University, 
Changsha 410008, China. FAU - Jiang, Na AU - Jiang N AD - Department of Gastroenterology, Xiangya Hospital, Central South University, 
Changsha 410008, China. FAU - Xu, Meihua AU - Xu M AD - Department of Gastroenterology, Xiangya Hospital, Central South University, 
Changsha 410008, China. LA - chi PT - Journal Article PL - China TA - Zhong Nan Da Xue Xue Bao Yi Xue Ban JT - Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences JID - 101230586 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp3 protein, mouse) RN - 0 (GATA3 Transcription Factor) RN - 0 (Gata3 protein, mouse) RN - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3) RN - 0 (T-Box Domain Proteins) RN - 0 (T-box transcription factor TBX21) RN - 3K9958V90M (Ethanol) RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) RN - 9PHQ9Y1OLM (Prednisolone) RN - EC 2.7.11.1 (Pim1 protein, mouse) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-pim-1) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Cell Differentiation MH - Colitis/chemically induced/*drug therapy/pathology MH - Colon/drug effects/pathology MH - Ethanol MH - Forkhead Transcription Factors/metabolism MH - GATA3 Transcription Factor/metabolism MH - Inflammatory Bowel Diseases/chemically induced/*drug therapy/pathology MH - Mice MH - Mice, Inbred BALB C MH - Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism MH - Prednisolone/pharmacology MH - Proto-Oncogene Proteins c-pim-1/*antagonists & inhibitors MH - Random Allocation MH - T-Box Domain Proteins/metabolism MH - T-Lymphocytes, Regulatory/cytology MH - Trinitrobenzenesulfonic Acid EDAT- 2018/06/11 06:00 MHDA- 2018/11/07 06:00 CRDT- 2018/06/11 06:00 PHST- 2018/06/11 06:00 [entrez] PHST- 2018/06/11 06:00 [pubmed] PHST- 2018/11/07 06:00 [medline] AID - 10.11817/j.issn.1672-7347.2018.05.004 [doi] PST - ppublish SO - Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 May 28;43(5):481-489. doi: 10.11817/j.issn.1672-7347.2018.05.004.