Document Detail


Blockade of STAT3 by antisense oligonucleotide in TNBS-induced murine colitis.
MedLine Citation:
PMID:  17089128     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND AIMS: The expression of signal transducers and activators of transcription 3 (STAT3) is increased in Crohn's disease (CD), and nuclear translocated STAT3 is also found in the disease. However, the role of STAT3 protein on the pathogenesis of CD is not clear. This study was executed to investigate the role of STAT3 protein on the pathogenesis of trinitrobenzene sulfonic acid (TNBS)-induced colitis, the pathogenesis of which is CD-like. METHODS: TNBS-induced colitis was produced, and STAT3 antisense oligonucleotide was administrated intracolonically during the early phase of colitis. The mice were killed 7 days later, and the expressions of STAT3 and phosphorylated STAT3 were identified by Western blot and immunofluorescence. The lamina propria mononuclear cells (LPMCs) were isolated freshly, and the percent of cell death and the expressions of Bcl-2 and Bax in LPMCs were evaluated. Colonic tissue damage and the production of inflammatory cytokines were measured also. RESULTS: Administration of STAT3 antisense oligonucleotide effectively inhibited STAT3 expression and phosphorylation in inflamed colonic mucosa of colitis. The mice that were administered STAT3 antisense oligonucleotide showed less colonic tissue damage with decreased production of inflammatory cytokines such as TNF-alpha and INF-gamma in mucosa compared with that of those TNBS-induced colitis. Administration of STAT3 antisense oligonucleotide successfully induced apoptosis of LPMCs and counteracted the unbalanced expressions of Bcl-2 and Bax in LPMCs from colitis. CONCLUSIONS: STAT3 activation may play an important role in the inflammatory process of TNBS-induced colitis, and inhibiting STAT3 activation during the early phase of the inflammatory response may have a beneficial effect on the colitis.
Authors:
AiPing Bai; PinJin Hu; Jie Chen; Xin Song; Wei Chen; WenXin Peng; ZhiRong Zeng; Xiang Gao
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Publication Detail:
Type:  Journal Article     Date:  2006-11-07
Journal Detail:
Title:  International journal of colorectal disease     Volume:  22     ISSN:  0179-1958     ISO Abbreviation:  Int J Colorectal Dis     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-07-11     Completed Date:  2007-08-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607899     Medline TA:  Int J Colorectal Dis     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  625-35     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, The first affiliated hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Cell Separation
Colitis / chemically induced,  metabolism*,  pathology
Colon / drug effects,  pathology,  secretion
Cytokines / secretion
Inflammation
Intestinal Mucosa / drug effects,  pathology
Leukocytes, Mononuclear / drug effects
Male
Mice
Mice, Inbred BALB C
Oligonucleotides, Antisense / administration & dosage,  pharmacology*
Phosphoproteins / metabolism
STAT3 Transcription Factor / antagonists & inhibitors*
Trinitrobenzenesulfonic Acid
Weight Loss / drug effects
Chemical
Reg. No./Substance:
0/Cytokines; 0/Oligonucleotides, Antisense; 0/Phosphoproteins; 0/STAT3 Transcription Factor; 2508-19-2/Trinitrobenzenesulfonic Acid

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