期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 303, 期 6, 页码 L539-L549出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00389.2011
关键词
calcium entry; transient receptor potential; cation channel; store-operated channel; allergy
资金
- National Institutes of Health: National Institute of Environmental Health Sciences [ZO1-ES-101684, ZO1-ES-025043]
Yildirim E, Carey MA, Card JW, Dietrich A, Flake GP, Zhang Y, Bradbury JA, Rebolloso Y, Germolec DR, Morgan DL, Zeldin DC, Birnbaumer L. Severely blunted allergen-induced pulmonary Th2 cell response and lung hyperresponsiveness in type 1 transient receptor potential channel-deficient mice. Am J Physiol Lung Cell Mol Physiol 303: L539-L549, 2012. First published July 13, 2012; doi:10.1152/ajplung.00389.2011.-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.
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