Intramural Research Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
Am J Physiol Lung Cell Mol Physiol. 2012 Sep 15;303(6):L539-49. doi: 10.1152/ajplung.00389.2011. Epub 2012 Jul 13.
Transient receptor potential channels (TRPCs) are widely expressed and regulate Ca²⁺ entry in the cells that participate in the pathophysiology of airway hyperreactivity, inflammation, and remodeling. In vitro studies point to a role for TRPC1-mediated Ca²⁺ signaling in several of these cell types; however, physiological evidence is lacking. Here we identify TRPC1 signaling as proinflammatory and a regulator of lung hyperresponsiveness during allergen-induced pulmonary response. TRPC1-deficient (Trpc1(-/-)) mice are hyposensitive to methacholine challenge and have significantly reduced allergen-induced pulmonary leukocyte infiltration coupled with an attenuated T helper type 2 (Th2) cell response. Upon in vitro allergen exposure, Trpc1(-/-) splenocytes show impaired proliferation and T cell receptor-induced IL-2 production. A high number of germinal centers in spleens of Trpc1(-/-) mice and elevated levels of immunoglobulins in their serum are indicative of dysregulated B cell function and homeostasis. Thus we propose that TRPC1 signaling is necessary in lymphocyte biology and in regulation of allergen-induced lung hyperresponsiveness, making TRPC1 a potential target for treatment of immune diseases and asthma.
瞬时受体电位通道（TRPCs）广泛表达，并调节参与气道高反应性、炎症和重塑的病理生理学的细胞中的 Ca²⁺内流。体外研究表明，TRPC1 介导的 Ca²⁺信号在这些细胞类型中的几种中发挥作用；然而，缺乏生理证据。在这里，我们确定 TRPC1 信号作为炎症前信号，并在变应原诱导的肺反应期间调节肺高反应性。TRPC1 缺陷型（Trpc1（-/-））小鼠对乙酰甲胆碱挑战的敏感性降低，并且变应原诱导的肺白细胞浸润明显减少，同时 Th2 细胞反应减弱。在体外变应原暴露下，Trpc1（-/-）脾细胞显示增殖受损和 T 细胞受体诱导的 IL-2 产生减少。Trpc1（-/-）小鼠脾脏中的生发中心数量较多，血清中的免疫球蛋白水平升高，表明 B 细胞功能和稳态失调。因此，我们提出 TRPC1 信号在淋巴细胞生物学和调节变应原诱导的肺高反应性中是必需的，这使得 TRPC1 成为治疗免疫性疾病和哮喘的潜在靶点。
