Resistin-like molecule beta regulates innate colonic function: barrier integrity and inflammation susceptibility.
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.


CONCLUSIONS
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.
Hogan
Simon P
SP
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Seidu
Luqman
L
Blanchard
Carine
C
Groschwitz
Katherine
K
Mishra
Anil
A
Karow
Margaret L
ML
Ahrens
Richard
R
Artis
David
D
Murphy
Andrew J
AJ
Valenzuela
David M
DM
Yancopoulos
George D
GD
Rothenberg
Marc E
ME
D000818:Animals; D003092:Colitis / Q000209:etiology*; D003106:Colon / Q000502:physiology*; D006729:Hormones, Ectopic / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D000073718:Pancreatitis-Associated Proteins; D010539:Permeability; D011506:Proteins / Q000235:genetics
D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490253:Reg3b protein, mouse; C490255:Reg3g protein, mouse; C486522:Retnlb protein, mouse