Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells
Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells
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DOI：
10.1159/000447668
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发表时间：
2016-01-01
影响因子：
5.3
通讯作者：
Weitnauer, Michael
中科院分区：
文献类型：
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作者：
Mijok, Vedrana;Lasitschka, Felix;Weitnauer, Michael
内质网应激与慢性肺部炎性疾病有关。我们假设toll样受体（TLR）信号和内质网应激的联合激活可能会增加原本耐受的气道上皮细胞的炎症反应。事实上，内质网应激导致BEAS-2B和人原代支气管上皮细胞对病原体相关分子模式刺激的il - 6和il - 8产生的反应增加。内质网应激可提高p38和ERK MAP激酶的活性，药理抑制可抑制这些激酶的增强作用。未折叠蛋白应答信号的敲除表明，协同活性主要由PERK和ATF6负责。具体来说，PERK和ATF6介导MAPK激活增加，这是有效分泌细胞因子所必需的。我们得出结论，在气道上皮细胞内，TLR信号的联合激活和内质网应激介导的MAPK激活导致协同促炎活性。我们推测，各种慢性肺部疾病中存在的内质网应激可促进TLR信号传导，从而促进促炎细胞因子的产生，从而作为共刺激危险信号。(C) 2016 S. Karger AG，巴塞尔
Endoplasmic reticulum (ER) stress is associated with chronic pulmonary inflammatory diseases. We hypothesized that the combined activation of both Toll-like receptor (TLR) signaling and ER stress might increase inflammatory reactions in otherwise tolerant airway epithelial cells. Indeed, ER stress resulted in an increased response of BEAS-2B and human primary bronchial epithelial cells to pathogen-associated molecular pattern stimulation with respect to IL6 and IL8 production. ER stress elevated p38 and ERK MAP kinase activation, and pharmacological inhibition of these kinases could inhibit the boosting effect. Knockdown of unfolded protein response signaling indicated that mainly PERK and ATF6 were responsible for the synergistic activity. Specifically, PERK and ATF6 mediated increased MAPK activation, which is needed for effective cytokine secretion. We conclude that within airway epithelial cells the combined activation of TLR signaling and ER stress-mediated MAPK activation results in synergistic proinflammatory activity. We speculate that ER stress, present in various chronic pulmonary diseases, boosts TLR signaling and therefore pro inflammatory cytokine production, thus acting as a costimulatory danger signal. (C) 2016 S. Karger AG, Basel