Linkage to peroxisome proliferator-activated receptor-γ in SAMP1/YitFc mice and in human Crohn’s disease

Sugawara, Kazuhiko; Olson, Timothy S.; Moskaluk, Christopher A.; Stevens, Brian K.; Hoang, Sharon B.; Kozaiwa, Kosuke; Cominelli, Fabio; Ley, Klaus; McDuffie, Marcia

doi:10.1053/j.gastro.2004.11.001

Cited by 82 publications

(76 citation statements)

References 37 publications

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“…We have used this model to look for markers of efficacy rather than total resolution of inflammation and clinical signs. We would like to evaluate the efficacy of S. thermophilus NCIMB 41856 to reduce signs of colitis in a spontaneous mouse model of colitis, such as the SAMP1/YitFc mouse (Matsumoto et al, 1998;Sugawara et al, 2005) or the recently developed Winnie mouse (Heazlewood et al, 2008). This will allow us to further investigate parameters such as the cytokine inflammatory profile in models more comparable to the naturally-occurring disease.…”

Section: Discussionmentioning

confidence: 99%

Streptococcus thermophilus NCIMB 41856 ameliorates signs of colitis in an animal model of inflammatory bowel disease

Bailey

Vince²,

Williams³

et al. 2017

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Treatment of inflammatory bowel disease (IBD) is mainly based on suppression of symptoms, often with numerous side effects. Trials of probiotics in IBD have frequently produced disappointing results. The majority of probiotics are unusual, since they do not require iron for growth, unlike many bacteria resident in the intestine. The IBD intestine is iron-rich due to bleeding and use of oral iron supplements; conventional probiotics would be rapidly outcompeted. We have evaluated an iron-responsive Streptococcus thermophilus strain for its potential to reduce signs of colitis. Efficacy of S. thermophilus was evaluated in the dextran sodium sulphate mouse model of colitis. Treated animals were given 1×108 cfu S. thermophilus per day and clinical observations were taken daily. At termination, gross and histopathological signs of disease, cellular infiltration, location of bacteria, and cytokine expression in the intestine were determined. S. thermophilus delayed onset of colitis and reduced clinical signs of disease, including bodyweight loss and gastrointestinal bleeding. It reduced bacterial translocation into the colonic tissue. Increased numbers of CD8+ intraepithelial lymphocytes were seen in control animals treated with S. thermophilus. S. thermophilus had no effect on gross pathology, histopathology or cytokine production in either colitic or control animals. We propose that S. thermophilus promotes maintenance of mucosal barrier function which reduces bacterial translocation, thereby reducing immune stimulation and associated inflammation. This allows mucosal healing, reducing gastrointestinal bleeding and weight loss. This could be studied as a locally-acting adjunct or alternative to current IBD treatments.

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Section: Discussionmentioning

confidence: 99%

Streptococcus thermophilus NCIMB 41856 ameliorates signs of colitis in an animal model of inflammatory bowel disease

Bailey

Vince²,

Williams³

et al. 2017

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“…First, the expression of PPAR-␥ in the colonic mucosa is shut down during severe inflammatory responses in experimental models of colitis and in patients with ulcerative colitis (52). In addition, rare alleles of PPAR-␥ have been found in patients with Crohn's disease (58). Thus, decreased levels of PPAR-␥ could result in impaired Treg activity and consequently in the prolongation of the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor γ Is Required for Regulatory CD4+ T Cell-Mediated Protection against Colitis

Hontecillas

Bassaganya‐Riera

2007

The Journal of Immunology

143

141

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Peroxisome proliferator-activated receptor (PPAR) γ activation has been implicated in the prevention of immunoinflammatory disorders; however, the mechanisms of regulation of effector and regulatory CD4+ T cell functions by endogenously activated PPAR-γ remain unclear. We have used PPAR-γ-deficient CD4+ T cells obtained from tissue-specific PPAR-γ null mice (i.e., PPAR-γ fl/fl; MMTV-Cre+) to investigate the role of endogenous PPAR-γ on regulatory T cell (Treg) and effector CD4+ T cell function. Overall, we show that the loss of PPAR-γ results in enhanced Ag-specific proliferation and overproduction of IFN-γ in response to IL-12. These findings correlate in vivo with enhanced susceptibility of tissue-specific PPAR-γ null mice to trinitrobenzene sulfonic acid-induced colitis. Furthermore, the transfer of purified PPAR-γ null CD4+ T cells into SCID recipients results in enteric disease. To test the assertion that the deficiency of PPAR-γ in Treg impairs their ability to prevent effector T cell-induced colitis, we performed cotransfer studies. These studies demonstrate that PPAR-γ-expressing, but not PPAR-γ null Treg, prevent colitis induced by transfer of naive CD4+ T cells into SCID recipients. In line with these findings, the production of IFN-γ by spleen and mesenteric lymph node-derived CD4+ T cells was down-regulated following transfer of PPAR-γ-expressing, but not PPAR-γ null, Treg. In conclusion, our data suggest that endogenous PPAR-γ activation represents a Treg intrinsic mechanism of down-regulation of effector CD4+ T cell function and prevention of colitis.

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“…Studies have reported the therapeutic effects of ligands such as PPAR-γ in various animal models of colitis induced in different ways, including chemical compounds (27,28), bacteria (29), ischemia-reperfusion (30) and in chronic colitis occurring after the transfer of immunocompetent T cells in SCID mice (31) or spontaneously in IL-10-deficient mice (32) and in SAMP1/YitFc animals (33). Impaired expression of PPAR-γ was found in colon epithelial cells of UC patients.…”

Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine attenuates PPAR-γ antagonist-deteriorated oxazolone-induced colitis in mice

Zheng

Yang

et al. 2011

Mol Med Report

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Abstract. Tetramethylpyrazine (TMP) is suggested to have anti-inflammatory activity. The aim of this study was to determine the role of peroxisome proliferator activated receptor γ (PPAR-γ) signaling in the pharmacologic effect of TMP on oxazolone (OXZ)-induced colitis. TMP (80 mg/kg/day i.p.) was administered daily 48 h after intrarectal instillation of OXZ, with or without PPAR-γ inhibitor [bisphenol A diglycidyl ether (BADGE) 30 mg/kg] during the 4 days before sacrifice. The inflammatory response was assessed by the disease activity index, macroscopy, histology and myeloperoxidase (MPO) activity. Expression levels of PPAR-γ, NF-κB p65, COX-2, iNOS and TNF-α mRNA in colon mucosa were determined by FQ-PCR, levels of PPAR-γ and NF-κB p65 protein were analyzed by immunohistochemistry, and the total and phosphorylated levels of p38 MAPK were assessed by western blotting. TMP significantly attenuated the damage caused by OXZ and substantially reduced the rise in MPO activity, TNF-α, iNOS, NF-κB p65 and COX-2 expression, as well as the increase in PPAR-γ production; however, no changes in the activation of p38 MAPK were observed. Inhibition of PPAR-γ signaling aggravated inflammation of colon mucosa, and increased p38 phosphrylation. TMP counteracted the effect of inhibition of PPAR-γ. We suggest that the effect of TMP treatment in ulcerative colitis may be related to PPAR-γ signaling, but is independent of PPAR-γ.

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Linkage to peroxisome proliferator-activated receptor-γ in SAMP1/YitFc mice and in human Crohn’s disease

Cited by 82 publications

References 37 publications

Streptococcus thermophilus NCIMB 41856 ameliorates signs of colitis in an animal model of inflammatory bowel disease

Streptococcus thermophilus NCIMB 41856 ameliorates signs of colitis in an animal model of inflammatory bowel disease

Peroxisome Proliferator-Activated Receptor γ Is Required for Regulatory CD4+ T Cell-Mediated Protection against Colitis

Tetramethylpyrazine attenuates PPAR-γ antagonist-deteriorated oxazolone-induced colitis in mice

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