Matrix metalloproteinase 8 contributes to solubilization of IL-13 receptor α2 in vivo

Weiguo Chen, Yasuhiro Tabata, Aaron M. Gibson, Michael O. Daines, Manoj R. Warrier, Marsha Wills-Karp, Gurjit K. Khurana Hershey

Research output: Contribution to journalArticle

Abstract

Background: IL-13 receptor α2 (IL-13Rα2) is a high-affinity receptor for IL-13, a central mediator of allergic asthma. It acts predominantly as a decoy receptor but can also contribute to IL-13 responses under certain conditions. IL-13Rα2 exists in soluble and membrane forms, which can both bind IL-13 and modulate its activity. Yet the proteolytic processes that contribute to the generation of soluble IL-13Rα2 are largely unknown. Objective: We sought to investigate the role of matrix metalloproteinases (MMPs) in the generation of soluble IL-13Rα2. Methods: Acellular cleavage assays by MMPs were performed by using glutathione-S-transferase fusion proteins of murine or human IL-13Rα2. IL-13Rα2 stable-transfected cells were used for analysis of surface expression and release of soluble IL-13Rα2. Wild-type and MMP-8-deficient mice were used for analysis of allergen-induced airway hyperresponsiveness and solubilization of IL-13Rα2. Results: Among several MMPs tested, only MMP-8 cleaved IL-13Rα2. Treatment of transfected human or murine cells expressing high levels of surface IL-13Rα2 with MMP-8 resulted in release of soluble IL-13Rα2 into the supernatants, with a concomitant decrease in surface IL-13Rα2 levels. The IL-13Rα2 solubilized by MMP-8 retained IL-13 binding activity. In an asthma model MMP-8-deficient mice displayed increased airway hyperresponsiveness and decreased soluble IL-13Rα2 protein levels in bronchoalveolar lavage fluid compared with those seen in wild-type mice after house dust mite challenge. Conclusion: MMP-8 cleaves IL-13Rα2 in vitro and contributes to the solubilization of IL-13Rα2 in vivo.

Original languageEnglish (US)
Pages (from-to)625-632
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume122
Issue number3
DOIs
StatePublished - Sep 1 2008

    Fingerprint

Keywords

  • IL-13
  • IL-13 receptor α2
  • Matrix metalloproteinase 8

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this