Expression and regulation of CCR1 by airway smooth muscle cells in asthma.
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-alpha and, to a lesser extent, IFN-gamma 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.
Joubert
Philippe
P
Meakins-Christie Laboratories, McGill University, and Hôpital du Sacré-Coeur de Montréal, Research Center, Québec, Canada.
Lajoie-Kadoch
Stéphane
S
Welman
Mélanie
M
Dragon
Stephane
S
Létuvée
Séverine
S
Tolloczko
Barbara
B
Halayko
Andrew J
AJ
Gounni
Abdelilah Soussi
AS
Maghni
Karim
K
Hamid
Qutayba
Q
D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008926:Plicamycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D054389:Receptors, CCR1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation
C515300:CCR1 protein, human; D012333:RNA, Messenger; D054389:Receptors, CCR1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; D008926:Plicamycin; D002118:Calcium