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

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International Journal of Colorectal Disease Aims and scope Submit manuscript

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.

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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

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Authors and Affiliations

  1. Department of Gastroenterology, The first affiliated hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    AiPing Bai, PinJin Hu, Jie Chen, Xin Song, Wei Chen, WenXin Peng, ZhiRong Zeng & Xiang Gao

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  1. AiPing Bai
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Correspondence to PinJin Hu.

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Bai, A., Hu, P., Chen, J. et al. Blockade of STAT3 by antisense oligonucleotide in TNBS-induced murine colitis. Int J Colorectal Dis 22, 625–635 (2007). https://doi.org/10.1007/s00384-006-0229-z

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