Role of Resistin-Like Molecule (RELM)-946; in Allergic Airway Inflammation

A. Haczku1, S. Ying2, S. Kierstein1, Q. Meng2, L.D. McVay1, C.J. Corrigan2, G.D. Wu1

Author address: 

1 Medicine, University of PA School of Medicine, Philadelphia, PA 2 Guy's, King's & St. Thomas' School of Medicine, London, UNITED KINGDOM

Abstract: 

RATIONALE: RELM-β , a novel protein with both cytokine and hormone-like activities is produced under Th2-type immune regulation in the gut in mice. We hypothesized that this molecule is also involved in the pathogenesis of the allergic airway response. METHODS: In situ hybridization and immunocytochemistry was performed on endobronchial biopsies from asthmatic patients and normal controls. Human airway epithelial cells (A549) were cultured in the presence and absence of IL-13. Mice deficient in RELM-β and their wild-type littermates were sensitized and challenged with Aspergillus fumigatus (Af). Lung function, inflammatory cell and cytokine profile, expression of RELM-β protein and mRNA was investigated 12, 24 and 48h later. RESULTS: RELM-β mRNA and protein expression in the airway epithelium of asthmatic patients was markedly elevated. IL-13 treatment of A549 cells also induced RELM-β production. Af provocation of sensitized mice stimulated mRNA activation and release of IL-4, IL-5 and IL-13 (but not IFN-γ ) within 24h, and release of RELM-β 48h later. In addition to a massive influx of neutrophils and eosinophils after challenge, sensitized wild-type mice had a significant airway hyperresponsiveness to methacholine. Interestingly, in spite of the presence of airway inflammation, RELM-β deficient mice were impaired in their methacholine responsiveness after allergen challenge. CONCLUSIONS: RELM-β is increased in the airway epithelium of asthmatic patients and in mice sensitized and challenged with Af. Since there was diminished methacholine responsiveness but no reduction in inflammation in RELM-β deficient mice, this protein may play a direct role in altered airway smooth muscle function.
2006

abstract No: 

709

Full conference title: 

2006 American Academy of Allergy, Asthma, and Immunology Annual Meeting
    • AAAAI 2006 (62nd)