Resistin-like Molecule Beta Regulates Innate Colonic Function: Barrier Integrity and Inflammation Susceptibility

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2006 Jul 4

PMID 16815164

Citations 91

Authors

Simon P Hogan

Luqman Seidu

Carine Blanchard

Katherine Groschwitz

Anil Mishra

Margaret L Karow

Richard Ahrens

David Artis

Andrew J Murphy

David M Valenzuela

George D Yancopoulos

Marc E Rothenberg

Affiliations

Soon will be listed here.

Abstract

Background: Resistin-like molecule (RELM) beta is a cysteine-rich cytokine expressed in the gastrointestinal tract and implicated in insulin resistance and gastrointestinal nematode immunity; however, its function primarily remains an enigma.

Objective: We sought to elucidate the function of RELM-beta in the gastrointestinal tract.

Methods: We generated RELM-beta gene-targeted mice and examined colonic epithelial barrier function, gene expression profiles, and susceptibility to acute colonic inflammation.

Results: We show that RELM-beta is constitutively expressed in the colon by goblet cells and enterocytes and has a role in homeostasis, as assessed by alterations in colon mRNA transcripts and epithelial barrier function in the absence of RELM-beta. Using acute colonic inflammatory models, we demonstrate that RELM-beta has a central role in the regulation of susceptibility to colonic inflammation. Mechanistic studies identify that RELM-beta regulates expression of type III regenerating gene (REG) (REG3beta and gamma), molecules known to influence nuclear factor kappaB signaling.

Conclusions: These data define a critical role for RELM-beta in the maintenance of colonic barrier function and gastrointestinal innate immunity.

Clinical Implications: These findings identify RELM-beta as an important molecule in homeostatic gastrointestinal function and colonic inflammation, and as such, these results have implications for a variety of human inflammatory gastrointestinal conditions, including allergic gastroenteropathies.

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