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

Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1238-46. doi: 10.1152/ajplung.00301.2005. Epub 2006 Jan 20.


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-alpha and downregulated by IFN-gamma. Our data indicate that TNF-alpha upregulates IL-17BR mainly through nuclear factor-kappaB as assessed with the IkappaB kinase 2 inhibitor AS-602868. In addition, both IFN-gamma and dexamethasone are able to antagonize a TNF-alpha-induced IL-17BR increase in mRNA expression. The mitogen-activated protein kinase kinase inhibitor U0126 totally reversed the inhibition observed with IFN-gamma, 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-alphaI 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Humans
  • Interferon-gamma / pharmacology*
  • Interleukin-17 / physiology*
  • Mice
  • Muscle, Smooth / physiology*
  • RNA, Messenger / genetics
  • Receptors, Interleukin / drug effects
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / physiology*
  • Recombinant Proteins / pharmacology
  • Respiratory Physiological Phenomena
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Cytokines
  • Interleukin-17
  • RNA, Messenger
  • Receptors, Interleukin
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma