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

Ariel Munitz, Amanda Waddell, Luqman Seidu, Eric T. Cole, Richard Ahrens, Simon P. Hogan, Marc E. Rothenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Resistin-like molecule (Relm) α is a secreted protein and a hallmark signature gene for alternatively activated macrophages. Relm-α is highly induced by allergic inflammatory triggers and perceived to promote tissue repair. Yet the function of Relm-α remains unknown. Objective: We sough to determine the role of Relm-α in dextran sodium sulfate (DSS)-induced colonic injury. Methods: The cellular source of Relm-α 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-α was assessed. Relm-α was administered intraperitoneally, and the cellular recruitment to the peritoneum was assessed. Results: After innate intestinal stimulation with DSS, Relm-α 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-α coactivated IL-6 and TNF-α 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-α initiated cellular recruitment to the peritoneum, and Relm-α was able to induce eosinophil chemotaxis in vitro. Conclusions: These findings demonstrate a central proinflammatory role for Relm-α in colonic innate immune responses, identifying a novel pathway for regulation of macrophage activation.

Original languageEnglish
Pages (from-to)1200-1207.e1
JournalJournal of Allergy and Clinical Immunology
Volume122
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

Keywords

  • LPS
  • Resistin-like molecule α
  • colitis
  • eosinophils
  • inflammation
  • inflammatory bowel disease
  • macrophages

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