title: Resistin-like molecule alpha enhances myeloid cell activation and promotes colitis.
abstract: BACKGROUND
  Resistin-like molecule (Relm) alpha is a secreted protein and a hallmark signature gene for alternatively activated macrophages. Relm-alpha is highly induced by allergic inflammatory triggers and perceived to promote tissue repair. Yet the function of Relm-alpha remains unknown.
  
  
  OBJECTIVE
  We sough to determine the role of Relm-alpha in dextran sodium sulfate (DSS)-induced colonic injury.
  
  
  METHODS
  The cellular source of Relm-alpha was determined after oral DSS-induced colitis. Retnla(-/-) mice were generated, subjected to DSS treatment, and monitored for disease progression (clinical and histopathologic features). Cytokine production in the supernatants of ex vivo colon cultures, and of LPS-stimulated macrophages incubated with Relm-alpha was assessed. Relm-alpha was administered intraperitoneally, and the cellular recruitment to the peritoneum was assessed.
  
  
  RESULTS
  After innate intestinal stimulation with DSS, Relm-alpha was highly expressed by eosinophils and epithelial cells. Retnla gene-targeted mice were protected from DSS-induced colitis (eg, decreased diarrhea, rectal bleeding, colon shortening, disease score, and histopathologic changes). Relm-alpha coactivated IL-6 and TNF-alpha release and inhibited IL-10 release from LPS-activated bone marrow-derived macrophages. Consistent with these finding, colon cultures of DSS-treated Retnla(-/-) mice produced decreased IL-6 and increased IL-10 ex vivo. Furthermore, Retnla(-/-) mice had substantially decreased c-Jun N-terminal kinase phosphorylation in vivo. In vivo administration of Relm-alpha initiated cellular recruitment to the peritoneum, and Relm-alpha was able to induce eosinophil chemotaxis in vitro.
  
  
  CONCLUSIONS
  These findings demonstrate a central proinflammatory role for Relm-alpha in colonic innate immune responses, identifying a novel pathway for regulation of macrophage activation.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Munitz
authors.forename: Amanda
authors.initials: A
authors.lastname: Waddell
authors.forename: Luqman
authors.initials: L
authors.lastname: Seidu
authors.forename: Eric T
authors.initials: ET
authors.lastname: Cole
authors.forename: Richard
authors.initials: R
authors.lastname: Ahrens
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hogan
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002633:Chemotaxis / Q000187:drug effects / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D016264:Dextran Sulfate / Q000633:toxicity; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C413576:Retnla protein, mouse; D016264:Dextran Sulfate; D048031:JNK Mitogen-Activated Protein Kinases