Prostaglandin E(2) exerts homeostatic regulation of pulmonary vascular remodeling in allergic airway inflammation.
Prostaglandin E(2) exerts homeostatic regulation of pulmonary vascular remodeling in allergic airway inflammation.
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DOI：
10.4049/jimmunol.0902835
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Boyce JA
中科院分区：
文献类型：
--
作者：
Lundequist A;Nallamshetty SN;Xing W;Feng C;Laidlaw TM;Uematsu S;Akira S;Boyce JA
在小鼠气道疾病模型中，PG合成的非选择性抑制增加了炎症，但单个PG的作用尚未完全阐明。为了研究PGE 2在天然变应原诱导的小鼠气道炎症模型中的作用，我们使用了缺乏关键末端合成酶微粒体PGE 2合酶（mPGES）-1的小鼠。缺乏mPGES-1的小鼠（ptges-/-小鼠）和野生型C57 BL/6对照用低剂量的来自屋尘螨粉尘螨（Dermatophagoides farinae）的提取物鼻内激发。Der f治疗的ptges-/-小鼠支气管肺泡灌洗液中的PGE 2水平比野生型对照组低约80%。在ptges−/−小鼠中，Der f诱导的支气管血管嗜酸性粒细胞增多适度增强。这两种Der f处理的菌株显示出相似的血清IgE和IgG 1的增加，以及Der f刺激的脾细胞产生的Th 1，Th 2和Th 17细胞因子的水平相当。这些发现表明，mPGES-1衍生的PGE 2不是过敏原致敏或效应T细胞应答发展所必需的。出乎意料的是，在Der f处理的ptges−/−小鼠中，血管平滑肌细胞的数量和肺内血管的厚度都显著增加。这些血管变化被抑制的管理，稳定的前列腺素E2类似物16，16-二甲基前列腺素E2，或选择性激动剂的E-前列腺素（EP）1，EP 2，和EP 3受体，分别为PGE 2。因此，mPGES-1及其产物PGE 2在变应原诱导的肺部炎症期间保护肺血管免于重塑，并且这些作用可能由一种以上的EP受体介导。
Nonselective inhibition of PG synthesis augments inflammation in mouse models of airway disease, but the roles of individual PGs are not completely clarified. To investigate the role of PGE2 in a mouse model of airway inflammation induced by a natural allergen, we used mice lacking the critical terminal synthetic enzyme, microsomal PGE2 synthase (mPGES)-1. Mice lacking mPGES-1 (ptges−/− mice) and wild-type C57BL/6 controls were challenged intranasally with low doses of an extract derived from the house dust mite Dermatophagoides farinae (Der f). The levels of PGE2 in the bronchoalveolar lavage fluids of Der f-treated ptges−/− mice were ~80% lower than the levels in wild-type controls. Der f-induced bronchovascular eosinophilia was modestly enhanced in the ptges−/− mice. Both Der f-treated strains showed similar increases in serum IgE and IgG1, as well as comparable levels of Th1, Th2, and Th17 cytokine production by Der f-stimulated spleen cells. These findings indicated that mPGES-1-derived PGE2 was not required for allergen sensitization or development of effector T cell responses. Unexpectedly, the numbers of vascular smooth muscle cells and the thickness of intrapulmonary vessels were both markedly increased in the Der f-treated ptges−/− mice. These vascular changes were suppressed by the administration of the stable PGE2 analog 16, 16-dimethyl PGE2, or of selective agonists of the E-prostanoid (EP) 1, EP2, and EP3 receptors, respectively, for PGE2. Thus, mPGES-1 and its product, PGE2, protect the pulmonary vasculature from remodeling during allergen-induced pulmonary inflammation, and these effects may be mediated by more than one EP receptor.
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影响因子：
15.3
作者：
Daley, Eleen;Emson, Claire;Guignabert, Christophe;Malefyt, Rene de Waal;Louten, Jennifer;Kurup, Viswanath P.;Hogaboam, Cory;Taraseviciene-Stewart, Laimute;Voelkel, Norbert F.;Rabinovitch, Marlene;Grunig, Ekkehard;Grunig, Gabriele
通讯作者：
Grunig, Gabriele
影响因子：
20.3
作者：
Chizzolini, Carlo;Chicheportiche, Rachel;Dayer, Jean-Michel
通讯作者：
Dayer, Jean-Michel
DOI：
10.1164/rccm.200308-1094oc
发表时间：
2004-02-01
影响因子：
24.7
作者：
Johnson, JR;Wiley, RE;Jordana, M
通讯作者：
Jordana, M
影响因子：
4.4
作者：
Martin, JG;Suzuki, M;Powell, WS
通讯作者：
Powell, WS
影响因子：
4.4
作者：
Claveau, D;Sirinyan, M;Mancini, JA
通讯作者：
Mancini, JA