Cytokine regulation of IL-13Ralpha2 and IL-13Ralpha1 in vivo and in vitro

J Allergy Clin Immunol. 2003 Apr;111(4):720-8. doi: 10.1067/mai.2003.1383.

Abstract

Background: IL-13 signals via a high-affinity receptor that includes IL-4Ralpha and IL-13Ralpha1 and binds to the decoy receptor IL-13Ralpha2. 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 T(H)2 and T(H)1 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-13Ralpha1 and IL-13Ralpha2 in lungs from lung targeted overexpression mice and lung fragments and cells in culture.

Results: IL-13Ralpha2 and IL-13Ralpha1 mRNA were detected at modest levels in lungs from control mice. In contrast, transgenic IL-13 caused a marked increase in IL-13Ralpha2 and IL-13Ralpha1 mRNA; this was most prominent in airway epithelial cells and macrophages. The effects of IL-13 on IL-13Ralpha2 were associated with comparable increases in protein production and were mediated by a blood leukocyte-independent and IL-4Ralpha-dependent mechanism. IL-13 stimulation of IL-13Ralpha1 was mediated via a blood leukocyte-dependent and partially IL-4Ralpha-dependent pathway. These effects were not specific for IL-13, because transgenic IL-4, IL-10, and IFN-gamma also stimulated IL-13Ralpha2 mRNA accumulation while stimulating-not altering and inhibiting-IL-13Ralpha1 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-gamma had similar effects on IL-13Ralpha2 and/or IL-13Ralpha1 in epithelial cells and macrophages in in vitro culture.

Conclusion: IL-13Ralpha2 and IL-13Ralpha1 are highly regulated in vivo and in vitro. These regulatory events might control IL-13 responses at sites of inflammation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytokines / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Interferon-gamma / pharmacology
  • Interleukin-13 / pharmacology
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4 / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Organ Culture Techniques
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin-13

Substances

  • Cytokines
  • Il13ra1 protein, mouse
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Interleukin-4
  • Interferon-gamma