Thymic stromal lymphopoietin in cigarette smoke-exposed human airway smooth muscle.
Thymic stromal lymphopoietin in cigarette smoke-exposed human airway smooth muscle.
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DOI：
10.4049/jimmunol.1000252
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发表时间：
2010-09-01
期刊：
影响因子：
--
通讯作者：
Prakash YS
中科院分区：
文献类型：
--
作者：
Smelter DF;Sathish V;Thompson MA;Pabelick CM;Vassallo R;Prakash YS
胸腺基质淋巴细胞生成素（TSLP）是一种新发现的IL-7样细胞因子，已知在哮喘和慢性阻塞性肺疾病患者的气道活检中表达。由于这两种疾病都可能因吸烟而诱发或加重，因此TSLP可能是香烟烟雾暴露与气道炎症信号传导之间的重要联系。在这方面，TSLP似乎也在气道平滑肌（ASM）中表达;然而，其作用尚不清楚。在目前的研究中，我们研究了TSLP和TSLP受体（TSLP-R）的表达和功能，在正常条件下，并在暴露于香烟烟雾提取物（CSE）的人ASM细胞。人ASM细胞的蛋白质印迹分析显示TSLP和TSLP-R的显著表达，通过过夜暴露于1或2%CSE，两者的表达增加。此外，CSE增加ASM释放TSLP。在平行实验中，使用酶促解离的人ASM细胞加载有Ca 2+指示剂fura 2-AM并使用荧光显微镜成像，我们评估了CSE暴露对激动剂刺激的细胞内Ca 2+（[Ca 2 +]i）响应的影响。[Ca2+]i对组胺的反应随着过夜CSE暴露而增加。暴露于TSLP也导致应答升高，其被TSLP和TSLP-R Ab钝化。重要的是，CSE对[Ca 2 +]i反应的增强作用也被这些Ab减弱。这些作用与CSE和TSLP诱导的STAT 5磷酸化变化相关。总的来说，这些新的数据表明，香烟烟雾，TSLP，和ASM的功能联系，香烟烟雾诱导的气道收缩性的增加可能是通过ASM的TSLP信号转导的增加介导的。
Thymic stromal lymphopoietin (TSLP) is a newly identified IL-7–like cytokine known to be expressed in airway biopsies of patients with asthma and chronic obstructive pulmonary disease. As both diseases may be induced or exacerbated by cigarette smoking, it is possible that TSLP represents an important link between cigarette smoke exposure and inflammatory signaling in the airways. In this regard, TSLP appears to also be expressed in airway smooth muscle (ASM); however, its role is unknown. In the current study, we examined TSLP and the TSLP receptor (TSLP-R) expression and function in human ASM cells under normal conditions and following exposure to cigarette smoke extract (CSE). Western blot analysis of human ASM cells showed significant expression of TSLP and TSLP-R, with increased expression of both by overnight exposure to 1 or 2% CSE. Furthermore, CSE increased TSLP release by ASM. In parallel experiments using enzymatically dissociated human ASM cells loaded with the Ca2+ indicator fura 2-AM and imaged using fluorescence microscopy, we evaluated the effects of CSE exposure on intracellular Ca2+ ([Ca2+]i) responses to agonist stimulation. [Ca2+]i responses to histamine were increased with overnight CSE exposure. Exposure to TSLP also resulted in elevated responses, which were blunted by TSLP and TSLP-R Abs. Importantly, the enhancing effects of CSE on [Ca2+]i responses were also blunted by these Abs. These effects were associated with CSE- and TSLP-induced changes in STAT5 phosphorylation. Overall, these novel data suggest that cigarette smoke, TSLP, and ASM are functionally linked and that cigarette smoke-induced increase in airway contractility may be mediated via ASM-derived increases in TSLP signaling.
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DOI：
10.4049/jimmunol.0804213
发表时间：
2009-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Stock P;Lombardi V;Kohlrautz V;Akbari O
通讯作者：
Akbari O
DOI：
10.4049/jimmunol.181.9.6557
发表时间：
2008-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zhou B;Headley MB;Aye T;Tocker J;Comeau MR;Ziegler SF
通讯作者：
Ziegler SF
TSLP和IL-7使用两种不同的机制来调节人CD4+ T细胞稳态。
影响因子：
15.3
作者：
Lu, Ning;Wang, Yi-Hong;Wang, Yui-Hsi;Arima, Kazuhiko;Hanabuchi, Shino;Liu, Yong-Jun
通讯作者：
Liu, Yong-Jun
DOI：
10.1111/j.1365-2222.2009.03241.x
发表时间：
2009-06
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
--
作者：
Wang YH;Liu YJ
通讯作者：
Liu YJ
影响因子：
3.3
作者：
Thomson, Neil C.;Chaudhuri, Rekha
通讯作者：
Chaudhuri, Rekha