Resistin-like molecule alpha enhances myeloid cell activation and promotes colitis

J Allergy Clin Immunol. 2008 Dec;122(6):1200-1207.e1. doi: 10.1016/j.jaci.2008.10.017.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / pathology
  • Chemotaxis / drug effects
  • Chemotaxis / genetics
  • Colitis / chemically induced
  • Colitis / genetics
  • Colitis / metabolism*
  • Colitis / pathology
  • Colon / metabolism
  • Colon / pathology
  • Cytokines / biosynthesis
  • Dextran Sulfate / toxicity
  • Eosinophils / metabolism
  • Eosinophils / pathology
  • Female
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation* / drug effects
  • Macrophage Activation* / genetics
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Organ Culture Techniques
  • Peritoneum / metabolism
  • Peritoneum / pathology
  • Phosphorylation / drug effects


  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Retnla protein, mouse
  • Dextran Sulfate
  • JNK Mitogen-Activated Protein Kinases