title: Resistin-like molecule beta (RELMbeta/FIZZ2) is highly expressed in the ileum of SAMP1/YitFc mice and is associated with initiation of ileitis.
abstract: SAMP1/Fc mice develop spontaneous ileitis that shares many features with human Crohn's disease. One of the earliest features of ileitis in SAMP1/Fc mice is an increase in the number of ileal goblet and intermediate cells. Resistin-like molecule beta (RELMbeta) is a goblet cell-specific, cysteine-rich peptide previously shown to function as part of the innate immune response. In this study, we examined the role of expression of RELMbeta in the initiation of ileal inflammation in SAMP1/Fc mice. RELMbeta was highly induced in the ilea of SAMP1/Fc mice beginning at age 5 wk, coincident with the histological appearance of inflammation. RELMbeta was found in ileal goblet cells and some intermediate and Paneth cells. Surprisingly, RELMbeta mRNA levels were significantly increased in the ilea of 80% of germ-free SAMP1/Fc mice examined compared with specific pathogen-free AKR control mice of similar age. Ileitis was observed in germfree SAMP1/Fc mice, although it was attenuated relative to specific pathogen-free SAMP1/Fc mice. These data suggest that neither the early induction of RELMbeta expression nor ileal inflammation requires the presence of viable intestinal flora. Neither was the induction of RELMbeta dependent on the major Th1 or Th2 cytokines. However, RELMbeta stimulated naive bone marrow-derived macrophages to secrete significant amounts of TNF-alpha, IL-6, and RANTES. Our data suggest that RELMbeta is involved in the initiation of ileitis in SAMP1/Fc mice and may act through the induction of proinflammatory cytokines from resident immune cells within the mucosa.
authors.affiliation: Digestive Health Center of Excellence, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Sean L
authors.initials: SL
authors.lastname: Barnes
authors.forename: Alda
authors.initials: A
authors.lastname: Vidrich
authors.forename: Mei-Lun
authors.initials: ML
authors.lastname: Wang
authors.forename: Gary D
authors.initials: GD
authors.lastname: Wu
authors.forename: Fabio
authors.initials: F
authors.lastname: Cominelli
authors.forename: Jesus
authors.initials: J
authors.lastname: Rivera-Nieves
authors.forename: Giorgos
authors.initials: G
authors.lastname: Bamias
authors.forename: Steven M
authors.initials: SM
authors.lastname: Cohn
mesh_terms: D000818:Animals; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology; D020397:Goblet Cells / Q000276:immunology* / Q000473:pathology; D006729:Hormones, Ectopic / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007079:Ileitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D019879:Paneth Cells / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D006729:Hormones, Ectopic; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; C486522:Retnlb protein, mouse