Conditional regulation of cyclooxygenase-2 in tracheobronchial epithelial cells modulates pulmonary immunity.
Conditional regulation of cyclooxygenase-2 in tracheobronchial epithelial cells modulates pulmonary immunity.
复制标题
气管支气管上皮细胞中环氧合酶-2 的条件调节可调节肺部免疫。
DOI：
10.1111/j.1365-2249.2007.03478.x
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发表时间：
2007
影响因子：
4.6
通讯作者：
Christman,JW
中科院分区：
文献类型：
--
作者：
Park,GY;Hu,N;Wang,X;Sadikot,RT;Yull,FE;Joo,M;PeeblesJr,RS;Blackwell,TS;Christman,JW
环氧合酶-2(COX-2)基因在肺组织中的表达在哮喘、肺炎等病理条件下被诱导，然而，COX-2基因在呼吸道中的表达在调节肺部炎症和免疫反应中的确切作用尚不清楚。为了确定可诱导的COX-2在呼吸道上皮细胞中的生理作用，我们开发了一种新的转基因小鼠，称为环氧合酶-2反式激活(COTA)小鼠，它在CC-10启动子的分布中过表达COX-2转基因，以响应多西环素。经多西环素治疗后，COX-2在COTA小鼠呼吸道上皮细胞中的表达增加，全肺组织中前列腺素E_2(PGE_2)、前列腺素D_2(PGD_2)、血栓素B_2(TXB_2)和6-酮前列腺素F_2受体(6-Keto Prostaglandin F2α，PGF_2α)的表达比野生型和未治疗的COTA小鼠增加3~7倍。有趣的是，来自COTA鼠的原代小鼠气管上皮细胞仅通过多西环素诱导的COX-2激活而产生PGE2，这提供了细胞特异性产生介质的迹象。在致敏阶段给予多西环素的卵清蛋白模型中，COTA小鼠肺组织中IL-4的水平高于未治疗的COTA小鼠和野生型小鼠。此外，与野生型小鼠相比，接受多西环素治疗的COTA小鼠对铜绿假单胞菌肺炎的清除受到损害。COX-2基因在呼吸道上皮细胞中的表达在决定对感染性和过敏性药物的免疫应答中起着重要作用。
Cyclooxygenase-2 (COX-2) gene expression in the lung is induced in pathological conditions such as asthma and pneumonia; however, the exact impact of COX-2 gene expression in the airway in regulating inflammatory and immunological response in the lung is not understood. To define a physiological role of inducible COX-2 in airway epithelial cells, we developed a novel line of transgenic mice, referred to asCycloOxygenase-2TransActivated (COTA) mice, that overexpress a COX-2 transgene in the distribution of the CC-10 promoter in response to doxycycline. In response to doxycycline treatment, COX-2 expression was increased in airway epithelium of COTA mice and whole lung tissue contained a three- to sevenfold increase in prostaglandin E2(PGE2), prostaglandin D2(PGD2) thromboxane B2(TXB2) and 6-Keto prostaglandin F2α(PGF2α) compared to wild-type and untreated COTA mice. Interestingly, primary mouse tracheal epithelial cells from COTA mice produced only PGE2by doxycycline-induced COX-2 activation, providing an indication of cellular specificity in terms of mediator production. In the ovalbumin model, in which doxycycline was given at the sensitization stage, there was an increase in interleukin (IL)-4 level in lung tissue from COTA mice compared to untreated COTA and wild-type mice. In addition, COTA mice that were treated with doxycycline had impaired clearance ofPseudomonas aeruginosapneumonia compared to wild-type mice. COX-2 gene expression in airway epithelial cells has an important role in determining immunological response to infectious and allergic agents.