Pim-1 inhibitor attenuates trinitrobenzene sulphonic acid induced colitis in the mice

Yueming Shen; Yuanhong Xie; Yan Zhao; Yan Long; Lingqian Li; Ya Zeng

doi:10.1016/j.clinre.2018.01.002

Pim-1 inhibitor attenuates trinitrobenzene sulphonic acid induced colitis in the mice

Clin Res Hepatol Gastroenterol. 2018 Sep;42(4):382-386. doi: 10.1016/j.clinre.2018.01.002. Epub 2018 Mar 16.

Authors

Yueming Shen¹, Yuanhong Xie², Yan Zhao³, Yan Long¹, Lingqian Li¹, Ya Zeng¹

Affiliations

¹ Department of Digestive Diseases, Changsha Central Hospital, No. 163, Shaoshan Nanlu, Changsha 410004, China.
² 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.
³ Department of Digestive Diseases, Changsha Central Hospital, No. 163, Shaoshan Nanlu, Changsha 410004, China. Electronic address: xxwn716@163.com.

PMID: 29551611
DOI: 10.1016/j.clinre.2018.01.002

Abstract

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.

Keywords: Inflammatory bowel diseases; Pim-1 kinase; Pim-1 kinase inhibitor; T-cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / drug effects
Colitis / drug therapy*
Colon / pathology
Disease Models, Animal
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / metabolism
GATA3 Transcription Factor / genetics
GATA3 Transcription Factor / metabolism
Inflammatory Bowel Diseases / drug therapy*
Mice, Inbred BALB C
Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
RNA, Messenger / metabolism
T-Lymphocytes / drug effects
T-Lymphocytes, Regulatory / drug effects
Trinitrobenzenesulfonic Acid / toxicity

Substances

Forkhead Transcription Factors
Foxp3 protein, mouse
GATA3 Transcription Factor
Gata3 protein, mouse
Nuclear Receptor Subfamily 1, Group F, Member 3
RNA, Messenger
Trinitrobenzenesulfonic Acid
Proto-Oncogene Proteins c-pim-1