title: Urocortins and CRF receptor type 2 variants in the male rat colon: gene expression and regulation by endotoxin and anti-inflammatory effect.
abstract: Urocortins (Ucns) 1, 2, and 3 and corticotropin-releasing factor receptor 2 (CRF2) mRNA are prominently expressed in various layers of the upper gut. We tested whether Ucns and CRF2 variants are also expressed in the different layers of the rat colon, regulated by LPS (100 μg/kg ip) and play a modulatory role in the colonic immune response to LPS. Transcripts of Ucns and CRF2b, the most common isoform in the periphery, were detected in all laser microdissected layers, including myenteric neurons. LPS increased the mRNA level of Ucn 1, Ucn 2, and Ucn 3 and decreased that of CRF2b in both the colonic mucosa and submucosa + muscle (S+M) layers at 2, 6, and 9 h after injection with a return to basal at 24 h. In addition, CRF2a, another variant more prominent in the brain, and a novel truncated splice variant CRF2a-3 mRNA were detected in all segments of the large intestine. LPS reciprocally regulated the colonic expression of these CRF2 variants by decreasing both CRF2a and CRF2b, while increasing CRF2a-3 in the mucosa and S+M. The CRF2 antagonist astressin2-B further enhanced LPS-induced increase of mRNA level of interleukin (IL)-1β, TNF-α, and inducible nitric oxide synthase in S+M layers and IL-1β in the mucosa and evoked TNF-α expression in the mucosa. These data indicate that Ucns/CRF2 variants are widely expressed in all colonic layers and reciprocally regulated by LPS. CRF2 signaling dampens the CD14/TLR4-mediated acute inflammatory response to Gram-negative bacteria in the colon.
authors.affiliation: Center for Neurobiology of Stress, Inflammatory Bowel Disease Center, CURE: Digestive Diseases Research Center, Digestive Diseases Division, Veterans Affairs Greater Los Angeles Healthcare System, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California pqyuan@mednet.ucla.edu.
authors.forename: Pu-Qing
authors.initials: PQ
authors.lastname: Yuan
authors.affiliation: Center for Neurobiology of Stress, Inflammatory Bowel Disease Center, CURE: Digestive Diseases Research Center, Digestive Diseases Division, Veterans Affairs Greater Los Angeles Healthcare System, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California.
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Wu
authors.affiliation: Center for Neurobiology of Stress, Inflammatory Bowel Disease Center, CURE: Digestive Diseases Research Center, Digestive Diseases Division, Veterans Affairs Greater Los Angeles Healthcare System, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California.
authors.forename: Charalabos
authors.initials: C
authors.lastname: Pothoulakis
authors.affiliation: Center for Neurobiology of Stress, Inflammatory Bowel Disease Center, CURE: Digestive Diseases Research Center, Digestive Diseases Division, Veterans Affairs Greater Los Angeles Healthcare System, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D003106:Colon / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D054832:Urocortins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C101531:CRF receptor type 2; D016207:Cytokines; D004731:Endotoxins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; C000607145:Ucn protein, rat; D054832:Urocortins; C528574:astressin-2B; C514216:urocortin 3, rat; D003346:Corticotropin-Releasing Hormone; D052247:Nitric Oxide Synthase Type II
keywords: astressin2-B; colon; corticotropin-releasing factor receptor type 2 variants; cytokines; lipopolysaccharide; urocortins