LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease

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2007
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Coste, Agnes
Dubuquoy, Laurent
Barnouin, Romain
Annicotte, Jean-Sebastien
Magnier, Benjamin
Notti, Mario
Corazza, Nadia
Antal, Maria Cristina
Metzger, Daniel
Desreumaux, Pierre
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Proceedings of the National Academy of Sciences. 2007, 104(32), pp. 13098-13103. ISSN 0027-8424. Available under: doi: 10.1073/pnas.0702440104
Zusammenfassung

Liver receptor homolog-1 (LRH-1) is a nuclear receptor involved in intestinal lipid homeostasis and cell proliferation. Here we show that haploinsufficiency of LRH-1 predisposes mice to the development of intestinal inflammation. Besides the increased inflammatory response, LRH-1 heterozygous mice exposed to 2,4,6-trinitrobenzene sulfonic acid show lower local corticosterone production as a result of an impaired intestinal expression of the enzymes CYP11A1 and CYP11B1, which control the local synthesis of corticosterone in the intestine. Local glucocorticoid production is strictly enterocytedependent because it is robustly reduced in epithelium-specific LRH-1-deficient mice. Consistent with these findings, colon biopsies of patients with Crohn’s disease and ulcerative colitis show reduced expression of LRH-1 and genes involved in the production of glucocorticoids. Hence, LRH-1 regulates intestinal immunity in response to immunological stress by triggering local glucocorticoid production. These findings underscore the importance of LRH-1 in the control of intestinal inflammation and the pathogenesis of inflammatory bowel disease. v

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Crohn’s disease, Inflammation, Nuclear receptors, Steroidogenesis, Ulcerative colitis
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ISO 690COSTE, Agnes, Laurent DUBUQUOY, Romain BARNOUIN, Jean-Sebastien ANNICOTTE, Benjamin MAGNIER, Mario NOTTI, Nadia CORAZZA, Maria Cristina ANTAL, Daniel METZGER, Pierre DESREUMAUX, Thomas BRUNNER, Johan AUWERX, Kristina SCHOONJANS, 2007. LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease. In: Proceedings of the National Academy of Sciences. 2007, 104(32), pp. 13098-13103. ISSN 0027-8424. Available under: doi: 10.1073/pnas.0702440104
BibTex
@article{Coste2007-08-07LRH1m-14272,
  year={2007},
  doi={10.1073/pnas.0702440104},
  title={LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease},
  number={32},
  volume={104},
  issn={0027-8424},
  journal={Proceedings of the National Academy of Sciences},
  pages={13098--13103},
  author={Coste, Agnes and Dubuquoy, Laurent and Barnouin, Romain and Annicotte, Jean-Sebastien and Magnier, Benjamin and Notti, Mario and Corazza, Nadia and Antal, Maria Cristina and Metzger, Daniel and Desreumaux, Pierre and Brunner, Thomas and Auwerx, Johan and Schoonjans, Kristina}
}
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