T(H)2 cytokines modulate the IL-9R expression on human neutrophils

Biochem Biophys Res Commun. 2009 Jun 26;384(2):167-72. doi: 10.1016/j.bbrc.2009.04.104. Epub 2009 May 3.

Abstract

Interleukin (IL)-9 is associated with key pathological features of asthma such as airway hyperresponsiveness, bronchoconstriction and mucus production. Inflammatory responses mediated by IL-9 rely on the expression of the IL-9R which has been reported on lung epithelial cells, T lymphocytes and recently on airway granulocyte infiltrates. In this study, we assessed the regulatory and constitutive cell surface expression of the IL-9Ralpha in unfractionated and purified human neutrophils from atopic asthmatics, atopic non-asthmatics and healthy normal controls. We demonstrate that T(H)2 cytokines (IL-4 or IL-13) and granulocyte macrophage-colony stimulating factor (GM-CSF) up-regulated mRNA and cell surface expression levels of the IL-9Ralpha in primary human and HL-60 differentiated neutrophils. Pharmacological inhibition of NF-kappaB did not affect T(H)2-mediated IL-9Ralpha expression in human neutrophils although IFN-gamma and IL-10 down-regulated IL-9Ralpha expression when co-incubated with IL-4, IL-13 or GM-CSF. Collectively, our results reveal a regulatory function for IFN-gamma and IL-10 on modulating the inducible IL-9Ralpha expression levels on peripheral blood neutrophils by T(H)2 cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / immunology
  • Cell Membrane / immunology
  • Cytokines / metabolism*
  • HL-60 Cells
  • Humans
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Neutrophils / immunology*
  • Receptors, Interleukin-9 / biosynthesis*
  • Receptors, Interleukin-9 / genetics
  • Th2 Cells / immunology*
  • Up-Regulation

Substances

  • Cytokines
  • NF-kappa B
  • Receptors, Interleukin-9