Apolipoprotein E is a concentration-dependent pulmonary danger signal that activates the NLRP3 inflammasome and IL-1β secretion by bronchoalveolar fluid macrophages from asthmatic subjects.
Apolipoprotein E is a concentration-dependent pulmonary danger signal that activates the NLRP3 inflammasome and IL-1β secretion by bronchoalveolar fluid macrophages from asthmatic subjects.
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载脂蛋白E是一种浓度依赖性的肺危险信号，可激活哮喘患者支气管肺泡液巨噬细胞NLRP3炎性体和IL-1β分泌。
DOI：
10.1016/j.jaci.2019.02.027
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发表时间：
2019-08
影响因子：
14.2
通讯作者：
Levine, Stewart J.
中科院分区：
文献类型：
--
作者：
Gordon, Elizabeth M.;Yao, Xianglan;Xu, Haitao;Karkowsky, William;Kaler, Maryann;Kalchiem-Dekel, Or;Barochia, Amisha V.;Gao, Meixia;Keeran, Karen J.;Jeffries, Kenneth R.;Levine, Stewart J.
屋尘螨（HDM）攻击Apoe - / -小鼠表现出增强的气道高反应性和粘膜细胞化生。表征哮喘巨噬细胞诱导APOE表达的途径，并确定APOE如何调节IL-1β的分泌。从哮喘支气管肺泡灌洗液（BALF）中分离巨噬细胞，从THP-1细胞和人单核细胞中提取。hdm衍生的半胱氨酸和丝氨酸蛋白酶通过蛋白酶激活受体2诱导哮喘BALF巨噬细胞分泌APOE。APOE浓度< 2.5 nM，与健康成人上皮衬里液（ELF）中的水平相似，不诱导哮喘BALF巨噬细胞释放IL-1β。相反，浓度≥25 nM的APOE诱导哮喘BALF巨噬细胞NLRP3和pro-IL-1β的表达，以及细胞分泌的caspase-1介导的成熟IL-1β的产生。HDM与APOE协同作用，启动和激活NLRP3炎性体。在HDM和poly（I:C）诱导的小鼠中性粒细胞气道炎症模型中，APOE在ELF中的浓度达到32 nM，并伴有BALF IL-1β的升高。巨噬细胞中apoe依赖性NLRP3炎性体激活主要由钾外排依赖机制介导。APOE可以作为内源性的、浓度依赖性的肺危险信号，启动并激活哮喘BALF巨噬细胞的NLPR3炎性小体分泌IL-1β。这可能代表了一种机制，当肺中的APOE浓度高于正常水平时，APOE会放大肺部炎症反应，这可能发生在屋尘螨引起的以中性粒细胞气道炎症为特征的哮喘病毒加重期间。载脂蛋白E是肺中浓度依赖性的危险信号，可启动并激活哮喘巨噬细胞NLRP3炎性小体分泌IL-1β。当肺部APOE浓度高于正常水平时，可能会促进和扩大炎症。
House dust mite (HDM)-challenged Apoe−/− mice display enhanced airway hyperreactivity and mucous cell metaplasia. To characterize the pathways that induce APOE expression by asthmatic macrophages and identify how APOE regulates IL-1β secretion. Macrophages were isolated from asthmatic bronchoalveolar lavage fluid (BALF) and derived from THP-1 cells and human monocytes. HDM-derived cysteine and serine proteases induced APOE secretion from asthmatic BALF macrophages via protease-activated receptor 2. APOE at concentrations of < 2.5 nM, which are similar to levels found in epithelial lining fluid (ELF) from healthy adults, did not induce IL-1β release from asthmatic BALF macrophages. In contrast, APOE at concentrations ≥ 25 nM induced NLRP3 and pro-IL-1β expression by asthmatic BALF macrophages, as well as the caspase-1-mediated generation of mature IL-1β that was secreted from cells. HDM acted synergistically with APOE to both prime and activate the NLRP3 inflammasome. In a murine model of neutrophilic airway inflammation induced by HDM and poly(I:C), APOE reached a concentration of 32 nM in ELF with associated increases in BALF IL-1β. APOE-dependent NLRP3 inflammasome activation in macrophages was primarily mediated by a potassium efflux-dependent mechanism. APOE can function as an endogenous, concentration-dependent pulmonary danger signal that primes and activates the NLPR3 inflammasome in asthmatic BALF macrophages to secrete IL-1β. This may represent a mechanism by which APOE amplifies pulmonary inflammatory responses when concentrations in the lung are increased above normal levels, which may occur during viral exacerbations of house dust mite-induced asthma characterized by neutrophilic airway inflammation. Apolipoprotein E is a concentration-dependent danger signal in the lung that can prime and activate the NLRP3 inflammasome in asthmatic macrophages to secrete IL-1β. This may promote and amplify inflammation when pulmonary APOE concentrations are increased above normal levels.
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影响因子：
10
作者：
Jacobsen NR;Møller P;Jensen KA;Vogel U;Ladefoged O;Loft S;Wallin H
通讯作者：
Wallin H
影响因子：
3
作者：
Chuang, Kelley;Elford, Erica L.;Tseng, Jill;Leung, Briana;Harris, Hobart W.
通讯作者：
Harris, Hobart W.
DOI：
10.1186/1476-9255-7-34
发表时间：
2010-07-22
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Arunachalam G;Sundar IK;Hwang JW;Yao H;Rahman I
通讯作者：
Rahman I
影响因子：
15.9
作者：
Hansmann, Georg;de Jesus Perez, Vinicio A.;Rabinovitch, Marlene
通讯作者：
Rabinovitch, Marlene
影响因子：
6
作者：
De Alba, Jorge;Otal, Raquel;Miralpeix, Montserrat
通讯作者：
Miralpeix, Montserrat