Maresin-1 reduces the pro-inflammatory response of bronchial epithelial cells to organic dust.
Maresin-1 reduces the pro-inflammatory response of bronchial epithelial cells to organic dust.
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DOI：
10.1186/1465-9921-14-51
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发表时间：
2013-05-10
影响因子：
5.8
通讯作者：
Romberger DJ
中科院分区：
文献类型：
--
作者：
Nordgren TM;Heires AJ;Wyatt TA;Poole JA;LeVan TD;Cerutis DR;Romberger DJ
接触有机粉尘会引起有害的气道炎症。目前的预防和治疗措施不能充分治疗由此产生的疾病，需要新的治疗干预措施。最近发现的来自多不饱和脂肪酸的介质具有抗炎和促溶解作用。我们测试了其中一种介质，maarein -1 （MaR1）在减少有机粉尘相关气道炎症中的潜力。由于支气管上皮细胞（BECs）在启动有机粉尘诱导的炎症中起关键作用，我们研究了MaR1对人BEC细胞系（BEAS-2B）的体外影响。细胞用0-200 nM的MaR1预处理1小时，然后用5%的猪禁闭设施衍生的有机粉尘提取物（HDE）处理1 - 24小时。另一种方法是利用小鼠肺切片模型进行支持性细胞因子研究。收集上清液，通过酶联免疫吸附法测定细胞因子水平。通过放射性检测评估上皮细胞蛋白激酶C （PKC）亚型α和λ，以及PKA活性，并利用荧光素酶载体报告研究NFκB和mapk相关信号机制。在HDE治疗BECs后，MaR1剂量依赖性地降低了IL-6和IL-8的产生。在小鼠肺切片模型中，在HDE治疗之前或之后给予MaR1也可以减少HDE刺激的细胞因子释放，包括TNF-α。先前的研究已经证实，HDE在1小时和6小时依次激活上皮细胞PKCα和PKCα，分别调节TNF-α、IL-6和IL-8的释放。MaR1预处理消除了hde诱导的PKC活性。此外，通过荧光素酶报告基因检测，24小时内HDE处理显示NFκB、AP-1、SP-1和SRE DNA结合活性在时间上增加。MaR1预处理没有改变NFκB、AP-1或SP-1的激活，但确实降低了SRE处DNA结合的激活。这些观察结果表明，MaR1在减弱BECs对有机粉尘提取物的促炎反应中发挥作用，其机制似乎不依赖于NFκB、AP-1或sp -1相关信号的减少，但可能部分通过sre相关信号介导。这些数据为MaR1在支气管上皮细胞中的新机制作用提供了见解，并支持未来的体内研究，以测试MaR1在减少环境粉尘暴露的有害炎症效应方面的效用。
Exposure to organic dust causes detrimental airway inflammation. Current preventative and therapeutic measures do not adequately treat resulting disease, necessitating novel therapeutic interventions. Recently identified mediators derived from polyunsaturated fatty acids exhibit anti-inflammatory and pro-resolving actions. We tested the potential of one of these mediators, maresin-1 (MaR1), in reducing organic dust-associated airway inflammation. As bronchial epithelial cells (BECs) are pivotal in initiating organic dust-induced inflammation, we investigated the in vitro effects of MaR1 on a human BEC cell line (BEAS-2B). Cells were pretreated for 1 hour with 0–200 nM MaR1, followed by 1–24 hour treatment with 5% hog confinement facility-derived organic dust extract (HDE). Alternatively, a mouse lung slice model was utilized in supportive cytokine studies. Supernatants were harvested and cytokine levels determined via enzyme-linked immunosorbent assays. Epithelial cell protein kinase C (PKC) isoforms α and ϵ, and PKA activities were assessed via radioactivity assays, and NFκB and MAPK-related signaling mechanisms were investigated using luciferase vector reporters. MaR1 dose-dependently reduced IL-6 and IL-8 production following HDE treatment of BECs. MaR1 also reduced HDE-stimulated cytokine release including TNF-α in a mouse lung slice model when given before or following HDE treatment. Previous studies have established that HDE sequentially activates epithelial PKCα and PKCϵ at 1 and 6 hours, respectively that regulated TNF-α, IL-6, and IL-8 release. MaR1 pretreatment abrogated these HDE-induced PKC activities. Furthermore, HDE treatment over a 24-hour period revealed temporal increases in NFκB, AP-1, SP-1, and SRE DNA binding activities, using luciferase reporter assays. MaR1 pretreatment did not alter the activation of NFκB, AP-1, or SP-1, but did reduce the activation of DNA binding at SRE. These observations indicate a role for MaR1 in attenuating the pro-inflammatory responses of BECs to organic dust extract, through a mechanism that does not appear to rely on reduced NFκB, AP-1, or SP-1-related signaling, but may be mediated partly through SRE-related signaling. These data offer insights for a novel mechanistic action of MaR1 in bronchial epithelial cells, and support future in vivo studies to test MaR1’s utility in reducing the deleterious inflammatory effects of environmental dust exposures.
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影响因子：
3.7
作者：
Hsiao HM;Sapinoro RE;Thatcher TH;Croasdell A;Levy EP;Fulton RA;Olsen KC;Pollock SJ;Serhan CN;Phipps RP;Sime PJ
通讯作者：
Sime PJ
影响因子：
64.8
作者：
Chiang, Nan;Fredman, Gabrielle;Backhed, Fredrik;Oh, Sungwhan F.;Vickery, Thad;Schmidt, Birgitta A.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
DOI：
10.1165/rcmb.2006-0047sf
发表时间：
2006-06-01
影响因子：
6.4
作者：
Mossman, Brooke T.;Lounsbury, Karen M.;Reddy, Sekhar P.
通讯作者：
Reddy, Sekhar P.
DOI：
10.1165/rcmb.2002-0206oc
发表时间：
2003-07-01
影响因子：
6.4
作者：
Liu, HW;Halayko, AJ;Solway, J
通讯作者：
Solway, J
5-HT，ACH和KCL诱导的钙振荡的频率决定了肺内支气管的平滑肌细胞的收缩。
影响因子：
3.8
作者：
Perez, Jose F;Sanderson, Michael J
通讯作者：
Sanderson, Michael J