International Journal of Colorectal Disease

, Volume 22, Issue 6, pp 625–635

Blockade of STAT3 by antisense oligonucleotide in TNBS-induced murine colitis

  • AiPing Bai
  • PinJin Hu
  • Jie Chen
  • Xin Song
  • Wei Chen
  • WenXin Peng
  • ZhiRong Zeng
  • Xiang Gao
Original Article

DOI: 10.1007/s00384-006-0229-z

Cite this article as:
Bai, A., Hu, P., Chen, J. et al. Int J Colorectal Dis (2007) 22: 625. doi:10.1007/s00384-006-0229-z

Abstract

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-α and INF-γ 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.

Keywords

STAT3Antisense oligonucleotideColitisLamina propria mononuclear cell

Abbreviations

ASON

antisense oligonucleotide

CD

Crohn’s disease

INF-γ

interferon γ

IL-6

interleukin-6

LPMCs

lamina propria mononuclear cells

MMAS

mismatch antisense oligonucleotide

MPO

myeloperoxidase

NF-κB

nuclear factor-kappa B

PMN

polymorphonuclear

pSTAT3

phosphorylated STAT3

STAT

signal transducers and activators of transcription

TNBS

trinitrobenzene sulfonic acid

TNF-α

tumor necrosis factor-α

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • AiPing Bai
    • 1
  • PinJin Hu
    • 1
  • Jie Chen
    • 1
  • Xin Song
    • 1
  • Wei Chen
    • 1
  • WenXin Peng
    • 1
  • ZhiRong Zeng
    • 1
  • Xiang Gao
    • 1
  1. 1.Department of GastroenterologyThe first affiliated hospital, Sun Yat-Sen UniversityGuangzhouChina