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Volume 09

Journal of Gastrointestinal & Digestive System

ISSN: 2161-069X

Gastro Congress 2019

July 08-09, 2019

conference

series

.com

July 08-09, 2019 | Zurich, Switzerland

14

th

Euro-Global Gastroenterology Conference

Page 20

Prema Robinson, J Gastrointest Dig Syst 2019, Volume 09

Genetic and small-molecule modulation of STAT3 in mouse models of inflammatory bowel

disease

Background &Aims

: Ulcerative colitis (UC) and Crohn’s disease (CD) are Inflammatory bowel diseases (IBD) of unclear

etiology that cause substantial morbidity and predispose to Colorectal-cancer (CRC). There are two isoforms of STAT3-α

and β; STAT3α is pro-inflammatory and anti-apoptotic, while STAT3β has opposing-effects on STAT3α. We determined

the contribution of STAT3 to UC and CD pathogenesis by comparing disease severity caused by dextran sodium sulfate

(DSS; UC model) or 2, 4, 6-trinitrobenzenesulfonic acid (TNBS; CDmodel) in mice expressing only STAT3α (∆

β

/∆

β

) and

in wild-type (WT) mice treated with TTI-101, a small-molecule inhibitor of both isoforms of STAT3.

Methods:

Seven days following administration of DSS in drinking water or two days following a single intra-rectal

administration of TNBS, ∆

β

/∆

β

mice, cage-control (+/+) mice and WT mice given TTI-101 or vehicle were examined for

IBD manifestations; their colons were evaluated for apoptosis of CD4

+

T cells, levels of STAT3 activation, IL-17A protein

expression and transcriptome alternations.

Results:

IBD manifestations were increased in ∆

β

/∆

β

transgenic vs. cage-control WT mice and were accompanied by

decreased apoptosis of colonic CD4

+

T cells. Complementing and extending these results, TTI-101 treatment of WTmice

prevented IBD, markedly increased apoptosis of colonic CD4

+

T cells, reduced colon levels of IL17A-producing cells and

down-modulated STAT3-gene targets involved in inflammation, apoptosis-resistance and colorectal-cancer metastases.

Conclusion:

STAT3, especially in CD4

+

T cells, contributes to the pathogenesis of UC and CD and its targeting may

provide a novel approach to disease treatment.

Biography

Prema Robinson is an Associate Professor since 2015 in the Department of Infectious Diseases, Infection Control and Employee Health, Division of Internal

Medicine in The University of Texas MD Anderson Cancer Center, USA.

PRobinson1@mdanderson.org

Prema Robinson

The University of Texas MD Anderson Cancer Center, USA