TY - JOUR
T1 - Expression and regulation of CCR1 by airway smooth muscle cells in asthma
AU - Joubert, Philippe
AU - Lajoie-Kadoch, Stéphane
AU - Welman, Mélanie
AU - Dragon, Stephane
AU - Létuvée, Séverine
AU - Tolloczko, Barbara
AU - Halayko, Andrew J.
AU - Gounni, Abdelilah Soussi
AU - Maghni, Karim
AU - Hamid, Qutayba
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2008/1/15
Y1 - 2008/1/15
N2 - C-C chemokines such as CCL11, CCL5, and CCL3 are central mediators in the pathogenesis of asthma. They are mainly associated with the recruitment and the activation of specific inflammatory cells, such as eosinophils, lymphocytes, and neutrophils. It has recently been shown that they can also activate structural cells, such as airway smooth muscle and epithelial cells. The aims of this study were to examine the expression of the CCL3 receptor, CCR1, on human airway smooth muscle cells (ASMC) and to document the regulation of this receptor by cytokines involved in asthma pathogenesis. We first demonstrated that CCR1 mRNA is increased in the airways of asthmatic vs control subjects and showed for the first time that ASMC express CCR1 mRNA and protein, both in vitro and in vivo. Calcium mobilization by CCR1 ligands confirmed its functionality on ASMC. Stimulation of ASMC with TNF-α and, to a lesser extent, IFN-γ resulted in an up-regulation of CCR1 expression, which was totally suppressed by both dexamethasone or mithramycin. Taken together, our data suggest that CCR1 might be involved in the pathogenesis of asthma, through the activation of ASMC by its ligands.
AB - C-C chemokines such as CCL11, CCL5, and CCL3 are central mediators in the pathogenesis of asthma. They are mainly associated with the recruitment and the activation of specific inflammatory cells, such as eosinophils, lymphocytes, and neutrophils. It has recently been shown that they can also activate structural cells, such as airway smooth muscle and epithelial cells. The aims of this study were to examine the expression of the CCL3 receptor, CCR1, on human airway smooth muscle cells (ASMC) and to document the regulation of this receptor by cytokines involved in asthma pathogenesis. We first demonstrated that CCR1 mRNA is increased in the airways of asthmatic vs control subjects and showed for the first time that ASMC express CCR1 mRNA and protein, both in vitro and in vivo. Calcium mobilization by CCR1 ligands confirmed its functionality on ASMC. Stimulation of ASMC with TNF-α and, to a lesser extent, IFN-γ resulted in an up-regulation of CCR1 expression, which was totally suppressed by both dexamethasone or mithramycin. Taken together, our data suggest that CCR1 might be involved in the pathogenesis of asthma, through the activation of ASMC by its ligands.
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U2 - 10.4049/jimmunol.180.2.1268
DO - 10.4049/jimmunol.180.2.1268
M3 - Article
C2 - 18178867
AN - SCOPUS:40449083278
SN - 0022-1767
VL - 180
SP - 1268
EP - 1275
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -