Immunoregulatory Actions of Epithelial Cell PPAR γ at the Colonic Mucosa of Mice with Experimental Inflammatory Bowel Disease

ABSTRACT Citrobacter rodentium is a classically noninvasive pathogen of mice that is similar to enteropathogenic Escherichia coli (EPEC) in man. Following oral infection of young mice, the organism colonizes the distal colon, and within 1 week the colonic mucosa doubles in thickness and there is massive epithelial cell hyperplasia. Since T-cell responses in mouse models of inflammatory bowel disease (IBD) also cause epithelial hyperplasia, we have investigated the possibility that C. rodentium promotes similar T-cell responses in the mucosa, thereby increasing epithelial shedding, transmission, and replication of the organism. Beginning 6 days after infection, bacteria were observed to be in close association with the epithelial surface and were also visible scattered throughout the lamina propria and in the submucosa. There was a CD3+-cell infiltrate into the colonic lamina propria and epithelium as well as mucosal thickening and crypt hyperplasia. The majority of CD3+ cells were CD4+ and were not γδ+. Reverse transcription-PCR analysis of cytokines also revealed a highly polarized Th1 response (interleukin-12, gamma interferon, and tumor necrosis factor alpha) in the mucosa and a large increase in the epithelial cell mitogen keratinocyte growth factor. None of the changes were seen in mice inoculated with bacteria lacking intimin (which is necessary for colonization), but they were seen in mice inoculated with C. rodentium complemented with intimin from EPEC. This is the first example of a classically noninvasive bacterial pathogen which elicits a strong mucosal Th1 response and which produces pathology similar to that seen in mouse models of IBD, which is also characterized by a strong Th1 response. These results also suggest that the colonic mucosa responds in a stereotypic way to Th1 responses.

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Activation of PPAR γ and δ by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease

Gastroenterology ◽

10.1053/j.gastro.2004.06.049 ◽

2004 ◽

Vol 127 (3) ◽

pp. 777-791 ◽

Cited By ~ 264

Author(s):

Josep Bassaganya-Riera ◽

Kathryn Reynolds ◽

Susan Martino-Catt ◽

Yongzhi Cui ◽

Lothar Hennighausen ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Bowel Disease ◽

Ppar Γ ◽

Experimental Inflammatory Bowel Disease ◽

Inflammatory Bowel

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Immunoregulatory mechanisms of macrophage PPAR-γ in mice with experimental inflammatory bowel disease

Mucosal Immunology ◽

10.1038/mi.2010.75 ◽

2010 ◽

Vol 4 (3) ◽

pp. 304-313 ◽

Cited By ~ 50

Author(s):

R Hontecillas ◽

W T Horne ◽

M Climent ◽

A J Guri ◽

C Evans ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Ppar Γ ◽

Experimental Inflammatory Bowel Disease ◽

Inflammatory Bowel ◽

Immunoregulatory Mechanisms

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Activation of autophagy and suppression of apoptosis by dapagliflozin attenuates experimental inflammatory bowel disease in rats: Targeting AMPK/mTOR, HMGB1/RAGE and Nrf2/HO-1 pathways

Chemico-Biological Interactions ◽

10.1016/j.cbi.2021.109368 ◽

2021 ◽

Vol 335 ◽

pp. 109368

Author(s):

Hany H. Arab ◽

Muhammad Y. Al-Shorbagy ◽

Muhammed A. Saad

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Experimental Inflammatory Bowel Disease ◽

Inflammatory Bowel

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Altered Leukotriene B4Metabolism in Colonic Mucosa with Inflammatory Bowel Disease

Scandinavian Journal of Gastroenterology ◽

10.3109/00365529509093234 ◽

1995 ◽

Vol 30 (1) ◽

pp. 44-49 ◽

Cited By ~ 16

Author(s):

A. Ikehata ◽

N. Hiwatashi ◽

Y. Kinouchi ◽

H. Yamazaki ◽

K. Ito ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Colonic Mucosa ◽

Inflammatory Bowel

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Chronic Nonspecific Inflammatory Bowel Disease of the Cecum and Proximal Colon in Children With Grossly Normal-Appearing Colonic Mucosa: Diagnosis by Colonoscopic Biopsies

PEDIATRICS ◽

10.1542/peds.80.2.255 ◽

1987 ◽

Vol 80 (2) ◽

pp. 255-261

Author(s):

Melvin B. Heyman ◽

Jay A. Perman ◽

Linda D. Ferrell ◽

M. Michael Thaler

Keyword(s):

Inflammatory Bowel Disease ◽

Abdominal Pain ◽

Bowel Disease ◽

Colonic Mucosa ◽

Disease Process ◽

Proximal Colon ◽

Chronic Abdominal Pain ◽

Medical Attention ◽

Inflammatory Bowel ◽

Inflammatory Changes

The diagnosis of inflammatory bowel disease rests on radiologic, endoscopic, and histologic creteria. Five patients, 2 to 17 years of age, sought medical attention because of chronic abdominal pain, diarrhea, and heme-positive stools. Rectal biopsies, visual inspection of colonic mucosa through the colonoscope, and contrast radiographs of the large and small intestine yielded nonspecific results. Serial endoscopic biopsies demonstrated a gradient of inflammatory changes diminishing in severity distally from the ileocecal valve and cecum. The disease process was most evident in specimens from the cecum, whereas biopsies distal to the transverse colon had a normal histologic appearance in all five patients. Biopsies from the proximal colon may provide evidence of inflammatory bowel disease not detectable using standard techniques. The combination of chronic abdominal pain, diarrhea, and heme-positive stools associated with inflammatory changes in biopsy specimens obtained from the proximal colon, but normal findings on radiologic, colonoscopic, and rectal biopsy examinations, may represent an early stage in the evolution of chronic nonspecific inflammatory bowel disease, including ulcerative colitis or regional enteritis (Crohn disease).

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