title: Expression of corticotropin releasing factor receptor type 1 (CRF1) in the human gastrointestinal tract and upregulation in the colonic mucosa in patients with ulcerative colitis.
abstract: Brain corticotropin-releasing factor (CRF) acting on CRF receptor type 1 (CRF(1)) is a main signaling pathway in the stress response. CRF is also produced in a variety of peripheral sites and acts locally as a proinflammatory mediator. We investigated CRF(1) mRNA expression in the human gastrointestinal tract, and localized CRF(1) immunoreactive cells in the colonic mucosa of healthy subjects and patients with ulcerative colitis (UC). In 4 male healthy subjects (24-29 years), CRF(1) transcript was detected by RT-PCR throughout the gastrointestinal tract with the highest levels in the ileum and rectum and the lowest level in the colon. Immunohistochemistry on whole thickness sigmoid colon sections showed that CRF(1) was localized in the lamina propria and epithelial cells and enteric neurons. In sigmoid colonic biopsies, immunohistochemically double-labeled cells with CRF(1) and CD163, a marker for macrophages, represent 79% of total CRF(1) immunoreactive (IR) cells in healthy subjects. In 10 UC patients, the total number of CRF(1) IR cells and CRF(1)/CD163 double-labeled macrophages was increased by 4.2 and 4.0 folds respectively compared to healthy subjects. These findings indicate that CRF(1) is distributed throughout the GI tract of healthy human subjects. The increase of CRF(1) IR cells prominently in macrophages of the sigmoid colonic mucosa of UC patients provides anatomical support for a role of CRF(1) signaling in modulating the immune-inflammatory process of UC.
authors.affiliation: CURE: Digestive Diseases Research Center and Center for Neurobiology of Stress, Digestive Diseases Division, Department of Medicine, University of California, Los Angeles, CA 90073, USA. pqyuan@mednet.ucla.edu
authors.forename: Pu-Qing
authors.initials: PQ
authors.lastname: Yuan
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Wu
authors.forename: Julie
authors.initials: J
authors.lastname: Elliott
authors.forename: Peter A
authors.initials: PA
authors.lastname: Anton
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Chatzaki
authors.forename: Mulugeta
authors.initials: M
authors.lastname: Million
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D005260:Female; D041981:Gastrointestinal Tract / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism*; D012016:Reference Values; D015854:Up-Regulation; D055815:Young Adult; D000098902:CD163 Antigen; D000099052:CRF Receptor, Type 1
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1