Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro

Tao Zheng, Zhou Zhu, Wei Liu, Chun Geun Lee, Qingsheng Chen, Robert J. Homer, Jack A. Elias

Research output: Contribution to journalArticlepeer-review

Abstract

Background: IL-13 signals via a high-affinity receptor that includes IL-4Rα and IL-13Rα1 and binds to the decoy receptor IL-13Rα2. The processes that regulate the expression of these receptor subunits, however, are poorly defined. Objective: These studies were designed to define the regulation of IL-13R components by TH2 and TH1 cytokines in vivo and in vitro. Methods: Northern analysis, in situ hybridization, RT-PCR analysis, and immunoprecipitation were used to define the expression of IL-13Rα1 and IL-13Rα2 in lungs from lung targeted overexpression mice and lung fragments and cells in culture. Results: IL-13Rα2 and IL-13Rα1 mRNA were detected at modest levels in lungs from control mice. In contrast, transgenic IL-13 caused a marked increase in IL-13Rα2 and IL-13Rα1 mRNA; this was most prominent in airway epithelial cells and macrophages. The effects of IL-13 on IL-13Rα2 were associated with comparable increases in protein production and were mediated by a blood leukocyte-independent and IL-4Rα-dependent mechanism. IL-13 stimulation of IL-13Rα1 was mediated via a blood leukocyte-dependent and partially IL-4Rα-dependent pathway. These effects were not specific for IL-13, because transgenic IL-4, IL-10, and IFN-γ also stimulated IL-13Rα2 mRNA accumulation while stimulating - not altering and inhibiting - IL-13Rα1 mRNA accumulation, respectively. These regulatory events were mediated, at least in part, by direct effects of these cytokines, because IL-13, IL-4, and IFN-γ had similar effects on IL-13Rα2 and/or IL-13Rα1 in epithelial cells and macrophages in in vitro culture. Conclusion: IL-13Rα2 and IL-13Rα1 are highly regulated in vivo and in vitro. These regulatory events might control IL-13 responses at sites of inflammation.

Original languageEnglish (US)
Pages (from-to)720-728
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume111
Issue number4
DOIs
StatePublished - Apr 1 2003

Keywords

  • Asthma
  • IL-10
  • IL-13 receptor
  • IL-13 transgenic mouse
  • IL-4
  • Interleukin 13
  • T2 cytokine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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