Lymphotoxin β receptor signaling induces IL-8 production in human bronchial epithelial cells.
Lymphotoxin β receptor signaling induces IL-8 production in human bronchial epithelial cells.
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淋巴毒素β受体信号传导在人支气管上皮细胞中诱导IL-8产生。
DOI：
10.1371/journal.pone.0114791
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yamauchi Y
中科院分区：
文献类型：
--
作者：
Mikami Y;Matsuzaki H;Horie M;Noguchi S;Jo T;Narumoto O;Kohyama T;Takizawa H;Nagase T;Yamauchi Y
由于吸入性皮质类固醇的使用，哮喘相关的死亡率一直在下降，但严重哮喘仍然是一个主要的临床问题。严重哮喘的一个特征是对类固醇治疗的抵抗，这与嗜酸性炎症有关。最近，肿瘤坏死因子超家族成员（TNFSF）14/LIGHT已被认为是严重哮喘气道炎症的关键介质。然而，由LIGHT在细胞中诱导的细胞因子/趋化因子产生的概况和细胞内机制知之甚少。我们的目的是阐明光诱导的细胞因子/趋化因子的产生的分子机制的支气管上皮细胞。人支气管上皮细胞表达LIGHT的受体-疱疹病毒进入介体（herpesvirus entry mediator），但不表达LIGHT的受体-光毒素β受体（LTβR）。LIGHT可诱导多种细胞因子/趋化因子，如白细胞介素（IL）-6、抑瘤素M、单核细胞趋化蛋白-1、生长调节蛋白α和IL-8。LTβR的特异性siRNA减弱BEAS-2B和正常人支气管上皮细胞产生IL-6和IL-8。LIGHT激活细胞内信号传导，如丝裂原活化蛋白激酶和核因子-κB（NF-κB）信号传导。LIGHT还诱导NF-κB反应元件的荧光素酶活性，但不诱导活化蛋白-1或血清反应元件的荧光素酶活性。细胞外信号调节激酶（Erk）磷酸化的特异性抑制剂和抑制剂κB的特异性抑制剂减弱了IL-8的产生，表明LIGHT-LTβR信号转导通过Erk和NF-κB途径诱导IL-8的产生。LIGHT可能通过LTβR信号传导，通过支气管上皮细胞产生细胞因子和趋化因子，导致气道嗜酸性炎症加重。
Asthma-related mortality has been decreasing due to inhaled corticosteroid use, but severe asthma remains a major clinical problem. One characteristic of severe asthma is resistance to steroid therapy, which is related to neutrophilic inflammation. Recently, the tumor necrosis factor superfamily member (TNFSF) 14/LIGHT has been recognized as a key mediator in severe asthmatic airway inflammation. However, the profiles and intracellular mechanisms of cytokine/chemokine production induced in cells by LIGHT are poorly understood. We aimed to elucidate the molecular mechanism of LIGHT-induced cytokine/chemokine production by bronchial epithelial cells. Human bronchial epithelial cells express lymphotoxin β receptor (LTβR), but not herpesvirus entry mediator, which are receptors for LIGHT. LIGHT induced various cytokines/chemokines, such as interleukin (IL)-6, oncostatin M, monocyte chemotactic protein-1, growth-regulated protein α and IL-8. Specific siRNA for LTβR attenuated IL-6 and IL-8 production by BEAS-2B and normal human bronchial epithelial cells. LIGHT activated intracellular signaling, such as mitogen-activated protein kinase and nuclear factor-κB (NF-κB) signaling. LIGHT also induced luciferase activity of NF-κB response element, but not of activator protein-1 or serum response element. Specific inhibitors of phosphorylation of extracellular signal-regulated kinase (Erk) and that of inhibitor κB attenuated IL-8 production, suggesting that LIGHT-LTβR signaling induces IL-8 production via the Erk and NF-κB pathways. LIGHT, via LTβR signaling, may contribute to exacerbation of airway neutrophilic inflammation through cytokine and chemokine production by bronchial epithelial cells.
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DOI：
10.1164/rccm.200507-1046oc
发表时间：
2006-03-15
影响因子：
24.7
作者：
Goleva, E;Li, LB;Leung, DYM
通讯作者：
Leung, DYM
影响因子：
24.3
作者：
Chung, Kian Fan;Wenzel, Sally E.;Teague, W. Gerald
通讯作者：
Teague, W. Gerald
DOI：
10.1124/jpet.112.201855
发表时间：
2013-10-01
影响因子：
3.5
作者：
Kaur, Manminder;Singh, Dave
通讯作者：
Singh, Dave
影响因子：
2.7
作者：
Feng E;Wan R;Yang S;Yan Z;Wang S;He W;Zhang Y;Yin H;Chen Z;Liu R
通讯作者：
Liu R
影响因子：
3.1
作者：
Godaly, G;Proudfoot, AEI;Agace, WW
通讯作者：
Agace, WW