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

Bai, Aiping; Hu, Pinjin; Chen, Jie; Song, Xin; Chen, Wei; Peng, WenXin; Zeng, Zhirong; Gao, Xiang

doi:10.1007/s00384-006-0229-z

Cited by 39 publications

(19 citation statements)

References 39 publications

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“…Indeed, activation of these pathways has been described in conjunction with dextran sulfate sodium-induced colitis in mice and TNBS-induced colitis in rodents (Bai et al, 2007;Kretzmann et al, 2008;Youn et al, 2009;Fitzpatrick et al, 2011b). Moreover, we have reported that Vido inhibits activation of these intracellular signaling pathways in the mouse colon and murine splenocytes (Fitzpatrick et al, 2011b).…”

Section: Discussionmentioning

confidence: 75%

Vidofludimus Inhibits Colonic Interleukin-17 and Improves Hapten-Induced Colitis in Rats by a Unique Dual Mode of Action

Fitzpatrick

Small

Doblhofer

et al. 2012

J Pharmacol Exp Ther

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Vidofludimus (Vido) is a novel oral immunomodulatory drug that inhibits dihydro-orotate dehydrogenase and lymphocyte proliferation in vitro. Vido inhibits interleukin (IL)-17 secretion in vitro independently of effects on lymphocyte proliferation. Our primary goal was to evaluate the in vivo effects of Vido on IL-17 secretion and the parameters of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. To further delineate the mechanism of action for Vido, rats were dosed concomitantly with uridine (Uri). Young Wistar rats received a 150-l enema of either phosphate-buffered saline (PBS) or TNBS on study day 1. The ex vivo effects of Vido on 24-h colonic IL-17 secretion were determined by using colonic strips from PBS-or TNBStreated rats. Some rats were dosed with vehicle, Vido, or Vido ϩ Uri for 6 days. On day 6, the parameters of colitis were determined from colonic tissue. These parameters included macroscopic, histological, and transcription factor measurements, IL-17 production, and numbers of CD3 ϩ T cells. Ex vivo Vido completely blocked IL-23 ϩ IL-1␤-stimulated secretion of IL-17 by colonic strips. In vivo Vido treatment alone most effectively reduced macroscopic and histological pathology and the numbers of CD3 ϩ T cells. In contrast, similarly reduced nuclear signal transducer and activator of transcription 3 (STAT3) binding and IL-17 levels were observed from animals treated with Vido alone and Vido ϩ Uri. Vido improves TNBS-induced colonic inflammation by a unique dual mode of action: 1) inhibiting expansion of colonic T lymphocytes, and 2) suppressing colonic IL-17 production, which is independent from the control of T-lymphocyte proliferation, by inhibition of STAT3 and nuclear factor-B activation.

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Section: Discussionmentioning

confidence: 75%

Vidofludimus Inhibits Colonic Interleukin-17 and Improves Hapten-Induced Colitis in Rats by a Unique Dual Mode of Action

Fitzpatrick

Small

Doblhofer

et al. 2012

J Pharmacol Exp Ther

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“…Moreover, STAT-3 and pSTAT-3 levels also correlate with the histologic profile of experimental inflammation tissues [48, 49]; therefore STAT-3 seems to be a potential therapeutic target for ulcerative colitis. In previous work, Bai et al [50] studied the blockade of STAT-3 by antisense oligonucleotides in trinitrobenzenesulphonic acid-(TNBS-)induced murine colitis. As can be seen in our results, in noncolitic animals, only weak immunoreactivity was detected in the nucleus for pSTAT-3 (Figure 9(c)).…”

Section: Resultsmentioning

confidence: 99%

Beneficial Effect of Shikonin on Experimental Colitis Induced by Dextran Sulfate Sodium in Balb/C Mice

Andújar

Rı́os

Giner

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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The naphthoquinone shikonin, a major component of the root of Lithospermum erythrorhizon, now is studied as an anti-inflammatory agent in the treatment of ulcerative colitis (UC). Acute UC was induced in Balb/C mice by oral administration of 5% dextran sodium sulfate (DSS). The disease activity index was evaluated, and a histologic study was carried out. Orally administered shikonin reduces induced UC in a dose-dependent manner, preventing the shortening of the colorectum and decreasing weight loss by 5% while improving the appearance of feces and preventing bloody stools. The disease activity index score was much lower in shikonin-treated mice than in the colitic group, as well as the myeloperoxidase activity. The expression of cyclooxygenase-2 was reduced by 75%, activation of NF-κB was reduced by 44%, and that of pSTAT-3 by 47%, as well as TNF-α, IL-1β, and IL-6 production. Similar results were obtained in primary macrophages culture. This is the first report of shikonin's ability to attenuate acute UC induced by DSS. Shikonin acts by blocking the activation of two major targets: NF-κB and STAT-3, and thus constitutes a promising potential therapeutic agent for the management of the inflammatory bowel disease.

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“…But, SA effectively controlled the activation of STAT3 in DSS‐induced mice (Figure ). STAT3 antisense oligonucleotide (Bai et al, ) or IL‐6 receptor‐mediated STAT3 activation blockade (Mitsuyama et al, ) was able to significantly enhance colonic inflammation in UC of murine models. Plant‐based natural agent has been previously reported to show protection against DSS‐induced UC by suppressing the activation of STAT3 (Sun et al, ).…”

Section: Discussionmentioning

confidence: 99%

The protective effect of syringic acid on dextran sulfate sodium‐induced experimental colitis in BALB/c mice

Fang

Zhu

Niu

et al. 2019

Drug Development Research

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Inflammatory bowel diseases involve chronic intestinal inflammation which is mostly caused by Crohn's disease and ulcerative colitis (UC) conditions. Patients having UC are prone to colorectal cancer and dysplastic polyps, and also have sporadic adenomas. Syringic acid (SA) possesses many health benefits including antioxidant, anti‐bacterial, and anti‐cancer. This study was aimed to identify the effects of SA on UC, using a murine experimental model. Clinical symptoms and weight loss were significantly reduced in mice induced with dextran sulfate sodium (DSS) and treated with SA, compared to untreated mice. The effects of SA exhibited in DSS‐induced mice were associated with significant decrease in the expressions levels of inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), pro‐inflammatory cytokines (tumor necrosis factor [TNF‐α], interleukin [IL‐1β and IL‐6]), remarkable amelioration of colonic architectural disruption, and a significant reduction in the activity of colonic myeloperoxidase. To further confirm the anti‐inflammatory property of SA, RAW 264.7 cells were stimulated with lipopolysaccharides. SA dose‐dependently inhibited the cytokines TNF‐α, IL‐1β, and IL‐6. It also decreased the expressions of p65‐NF‐κB and IκB, thus reducing the activation and nuclear accumulation of p‐STAT‐3Y705. This prohibited the degradation of inhibitory protein, IκB, as well as inhibited the nuclear translocation of p65‐NF‐κB in colonic tissue. It was concluded that SA has a potential to limit inflammation via inhibiting the p65‐NF‐κB and STAT3 signaling; hence it can be used for therapeutic purposes.

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

Abstract: 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.

Cited by 39 publications

References 39 publications

Vidofludimus Inhibits Colonic Interleukin-17 and Improves Hapten-Induced Colitis in Rats by a Unique Dual Mode of Action

Vidofludimus Inhibits Colonic Interleukin-17 and Improves Hapten-Induced Colitis in Rats by a Unique Dual Mode of Action

Beneficial Effect of Shikonin on Experimental Colitis Induced by Dextran Sulfate Sodium in Balb/C Mice

The protective effect of syringic acid on dextran sulfate sodium‐induced experimental colitis in BALB/c mice

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