Joubert Philippe, Lajoie-Kadoch Stéphane, Welman Mélanie, Dragon Stephane, Létuvée Séverine, Tolloczko Barbara, Halayko Andrew J, Gounni Abdelilah Soussi, Maghni Karim, Hamid Qutayba
Meakins-Christie Laboratories, McGill University, and Hôpital du Sacré-Coeur de Montréal, Research Center, Québec, Canada.
J Immunol. 2008 Jan 15;180(2):1268-75. doi: 10.4049/jimmunol.180.2.1268.
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.
C-C趋化因子如CCL11、CCL5和CCL3是哮喘发病机制中的核心介质。它们主要与特定炎症细胞（如嗜酸性粒细胞、淋巴细胞和中性粒细胞）的募集和激活有关。最近有研究表明，它们还能激活气道平滑肌和上皮细胞等结构细胞。本研究的目的是检测CCL3受体CCR1在人气道平滑肌细胞（ASMC）上的表达，并记录参与哮喘发病机制的细胞因子对该受体的调控作用。我们首先证明，与对照组相比，哮喘患者气道中CCR1 mRNA增加，并且首次表明ASMC在体外和体内均表达CCR1 mRNA和蛋白。CCR1配体引起的钙动员证实了其在ASMC上的功能。用肿瘤坏死因子-α（TNF-α）刺激ASMC，以及在较小程度上用干扰素-γ（IFN-γ）刺激，导致CCR1表达上调，而地塞米松或光神霉素可完全抑制这种上调。综上所述，我们的数据表明，CCR1可能通过其配体激活ASMC而参与哮喘的发病机制。
