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Molecular control of the glucocorticoid synthesis in the intestinal mucosa

English title Molecular control of the glucocorticoid synthesis in the intestinal mucosa
Applicant Brunner Thomas
Number 110030
Funding scheme Project funding (Div. I-III)
Research institution Institut für Pathologie Medizinische Fakultät Universität Bern
Institution of higher education University of Berne - BE
Main discipline Immunology, Immunopathology
Start/End 01.02.2006 - 31.01.2009
Approved amount 335'000.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Endocrinology

Keywords (6)

Endokrinologie; Steroide; Transkription; Genregulation; intestinales Immunsystem; Glucocorticoidsynthese

Lay Summary (English)

Lead
Lay summary
Glucocorticoids are steroid hormones that play an important role in regulation of immune cells and inflammation. Consequently, glucocortioids and synthetic derivatives are successfully used in the treatment of inflammatory diseases, including inflammatory bowel disease, such as Crohn’s Disease and Ulcerative Colitis. Until recently, the adrenal glands were considered the only source of glucocorticoids. However, recent evidence indicates that various other tissues are capable of synthesizing immunoregulatory glucocortiocids, including thymus, skin, brain and vasculature. We also have found that the intestinal epithelium is an important source of glucocorticoids. Intestinal epithelial cells synthesize glucococorticoids in response to local immune cell activation, and in turn control local immune responses. The aim of this study is to investigate how intestinal glucocorticoid synthesis is regulated. A major focus of the study is to understand how the activation of intestinal T cells triggers the synthesis of glucocorticoids in epithelial cells. We are thus examining factors released by activated T cells for their glucocorticoid-inducing activity in intestinal epithelial cells. Of major interest in this regards is the role of TNF?, as this pro-inflammatory cytokine has been previously implicated in deregulation of intestinal immune homeostasis and induction of inflammatory diseases of the intestinal mucosa. Furthermore, we are exploring the role of nuclear receptors in the transcriptional control of steroidogenic enzymes in intestinal epithelial cells. While SF-1 (Steroidogenic Factor-1) is a critical transcription factor for the regulation of steroidogenesis in the adrenal glands, it is absent in the intestine and seems to be functionally replaced by its close homolog LRH-1 (Liver Receptor Homolog-1). Experiments in intestinal epithelial cell lines and experimental mice models are also compared with tissue samples from patients with inflammatory bowel disease. Current data indicate a critical role for LRH-1 and glucocorticoids in the control of intestinal immune homeostasis and the pathogenesis of inflammatory bowel disease.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
121854 Regulation of intestinal glucocorticoid synthesis by EGF receptor-induced signaling pathways 01.02.2009 Project funding (Div. I-III)
65021 Characterization of glucocorticoid synthesis in the intestinal mucosa and its role in the regulation of intestinal immune responses 01.04.2002 Project funding (Div. I-III)

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