期刊
EUROPEAN RESPIRATORY JOURNAL
卷 40, 期 2, 页码 470-478出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00090511
关键词
Asthma; caveolae; cytokine; inflammation; Orai1; stromal interaction molecule 1
资金
- National Institutes of Health (NIH) [HL090595, HL090595-S2, HL088029, HL74309]
- Flight Attendant Medical Research Institute (FAMRI)
Caveolae, plasma membrane invaginations with constitutive caveolin proteins, harbour proteins involved in intracellular calcium ([Ca2+](i)) regulation. In human airway smooth muscle (ASM), store-operated Ca2+ entry (SOCE) is a key component of [Ca2+](i) regulation, and contributes to increased [Ca2+](i) in inflammation. SOCE involves proteins Orai1 and stromal interaction molecule (STIM)1. We investigated the link between caveolae, SOCE and inflammation in ASM. [Ca2+](i) was measured in human ASM cells using fura-2. Small interference RNA (siRNA) or overexpression vectors were used to alter expression of caveolin-1 (Cav-1), Orai1 or STIM1. Tumour necrosis factor (TNF)-alpha was used as a representative pro-inflammatory cytokine. TNF-alpha increased SOCE following sarcoplasmic reticulum Ca2+ depletion, and increased whole-cell and caveolar Orai1 (but only intracellular STIM1). Cav-1 siRNA decreased caveolar and whole-cell Orai1 (but not STIM1) expression, and blunted SOCE, even in the presence of TNF-alpha. STIM1 overexpression substantially enhanced SOCE: an effect only partially reversed by Cav-1 siRNA. In contrast, Orai1 siRNA substantially blunted SOCE even in the presence of TNF-alpha. Cav-1 overexpression significantly increased Orai1 expression and SOCE, especially in the presence of TNF-alpha. These results demonstrate that caveolar expression and regulation of proteins such as Orai1 are important for [Ca2+](i) regulation in human ASM cells and its modulation during inflammation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据