TY - JOUR
T1 - TNF-α and IFN-γ inversely modulate expression of the IL-17E receptor in airway smooth muscle cells
AU - Lajoie-Kadoch, Stéphane
AU - Joubert, Philippe
AU - Létuvé, Séverine
AU - Halayko, Andrew J.
AU - Martin, James G.
AU - Soussi-Gounni, Abdellilah
AU - Hamid, Qutayba
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/6
Y1 - 2006/6
N2 - 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.
AB - 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.
KW - Cytokine receptors
KW - Cytokines
KW - Extracellular matrix
KW - Human
KW - Interferon-γ
KW - Interleukin-17E
KW - Stromal cells
KW - Tumor necrosis factor-α
UR - http://www.scopus.com/inward/record.url?scp=33744806331&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33744806331&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00301.2005
DO - 10.1152/ajplung.00301.2005
M3 - Article
C2 - 16428271
AN - SCOPUS:33744806331
SN - 1040-0605
VL - 290
SP - L1238-L1246
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 6
ER -