TNF-α and IFN-γ inversely modulate expression of the IL-17E receptor in airway smooth muscle cells

Stéphane Lajoie-Kadoch, Philippe Joubert, Séverine Létuvé, Andrew J. Halayko, James G. Martin, Abdellilah Soussi-Gounni, Qutayba Hamid

Research output: Contribution to journalArticlepeer-review

Abstract

The interleukin-17B receptor (IL-17BR) is expressed in a variety of tissues and is upregulated under inflammatory conditions. This receptor binds both its cognate ligand IL-17B and IL-17E/IL-25, a novel cytokine known to promote Th2 responses. The present study shows that airway smooth muscle cells express IL-17BR in vitro and that its expression is upregulated by TNF-α and downregulated by IFN-γ. Our data indicate that TNF-α upregulates IL-17BR mainly through nuclear factor-κB as assessed with the IκB kinase 2 inhibitor AS-602868. In addition, both IFN-γ and dexamethasone are able to antagonize a TNF-α-induced IL-17BR increase in mRNA expression. The mitogen-activated protein kinase kinase inhibitor U0126 totally reversed the inhibition observed with IFN-γ, suggesting the involvement of the extracellular signal-regulated kinase pathway in this effect. In addition, on stimulation with IL-17E, airway smooth muscle cells increase their expression of ECM components, namely procollagen-αI and lumican mRNA. Furthermore, immunohistochemical analysis of biopsies from asthmatic subjects reveals that this receptor is abundant in smooth muscle layers. This is the first report showing IL-17BR receptor in structural cells of the airways. Our results suggest a potential proremodeling effect of IL-17E on airway smooth muscle cells through the induction of ECM and that its receptor is upregulated by proinflammatory conditions.

Original languageEnglish (US)
Pages (from-to)L1238-L1246
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume290
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

Keywords

  • Cytokine receptors
  • Cytokines
  • Extracellular matrix
  • Human
  • Interferon-γ
  • Interleukin-17E
  • Stromal cells
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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