Role for TAK1 in cigarette smoke-induced proinflammatory signaling and IL-8 release by human airway smooth muscle cells.
Role for TAK1 in cigarette smoke-induced proinflammatory signaling and IL-8 release by human airway smooth muscle cells.
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TAK1 在香烟烟雾诱导的促炎信号传导和人气道平滑肌细胞释放 IL-8 中的作用。
DOI：
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
H. Meurs
中科院分区：
文献类型：
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作者：
Tonio Pera;Claudia Atmaj;Marieke van der Vegt;A. Halayko;J. Zaagsma;H. Meurs
慢性阻塞性肺疾病（COPD）是一种炎症性疾病，其特征是肺功能进行性下降。慢性阻塞性肺病患者的气道平滑肌 (ASM) 质量可能会增加，导致气流受限和促炎细胞因子的产生。香烟烟雾 (CS) 是 COPD 的主要危险因素，会导致 ASM 细胞增殖以及白细胞介素 8 (IL-8) 诱导的中性粒细胞增多。在各种细胞类型中，转化生长因子-β 激活激酶 1 (TAK1) 在 MAP 激酶和 NF-κB 激活以及 IL-1β、TNF-α 和脂多糖诱导的 IL-8 释放中发挥着至关重要的作用。 TAK1 在 CS 诱导的 IL-8 释放中的作用尚不清楚。本研究的目的是探讨 TAK1 在 CS 诱导的 NF-κB 和 MAP 激酶信号传导以及人 ASM 细胞释放 IL-8 中的作用。用 CS 提取物 (CSE) 刺激这些细胞会增加 IL-8 释放和 ERK-1/2 磷酸化，以及 Iκ-Bα 降解和 p65 NF-κB 亚基磷酸化。使用特异性 TAK1 抑制剂 LL-Z-1640-2（5Z-7-oxozeaenol；100 nM）预处理可抑制 CSE 诱导的 ERK-1/2 磷酸化和 Iκ-Bα 降解。同样，显性失活 TAK1 的表达抑制 CSE 诱导的 ERK-1/2 磷酸化。此外，TAK1 和 NF-κB (SC-514；50 μM) 和 ERK-1/2 (U-0126；3 μM) 信号传导抑制剂可抑制 ASM 细胞 CSE 诱导的 IL-8 释放。这些数据表明 TAK1 在 CSE 诱导的 ERK-1/2 和 NF-κB 信号传导以及人 ASM 细胞释放 IL-8 中发挥重要作用。此外，他们将 TAK1 确定为抑制 CS 诱导的炎症反应的新靶点，该炎症反应涉及 COPD 的发生和进展。
Chronic obstructive pulmonary disease (COPD) is an inflammatory disease, characterized by a progressive decline in lung function. Airway smooth muscle (ASM) mass may be increased in COPD, contributing to airflow limitation and proinflammatory cytokine production. Cigarette smoke (CS), the major risk factor of COPD, causes ASM cell proliferation, as well as interleukin-8 (IL-8)-induced neutrophilia. In various cell types, transforming growth factor-β-activated kinase 1 (TAK1) plays a crucial role in MAP kinase and NF-κB activation, as well as IL-8 release induced by IL-1β, TNF-α, and lipopolysaccharide. The role of TAK1 in CS-induced IL-8 release is not known. The aim of this study was to investigate the role of TAK1 in CS-induced NF-κB and MAP kinase signaling and IL-8 release by human ASM cells. Stimulation of these cells with CS extract (CSE) increased IL-8 release and ERK-1/2 phosphorylation, as well as Iκ-Bα degradation and p65 NF-κB subunit phosphorylation. CSE-induced ERK-1/2 phosphorylation and Iκ-Bα degradation were both inhibited by pretreatment with the specific TAK1 inhibitor LL-Z-1640-2 (5Z-7-oxozeaenol; 100 nM). Similarly, expression of dominant-negative TAK1 inhibited CSE-induced ERK-1/2 phosphorylation. In addition, inhibitors of TAK1 and the NF-κB (SC-514; 50 μM) and ERK-1/2 (U-0126; 3 μM) signaling inhibited the CSE-induced IL-8 release by ASM cells. These data indicate that TAK1 plays a major role in CSE-induced ERK-1/2 and NF-κB signaling and in IL-8 release by human ASM cells. Furthermore, they identify TAK1 as a novel target for the inhibition of CS-induced inflammatory responses involved in the development and progression of COPD.
影响因子：
15.9
作者：
Brat, DJ;Bellail, AC;Van Meir, EG
通讯作者：
Van Meir, EG