A key role for prostaglandin I2 in limiting lung mucosal Th2, but not Th1, responses to inhaled allergen
A key role for prostaglandin I2 in limiting lung mucosal Th2, but not Th1, responses to inhaled allergen
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DOI：
10.4049/jimmunol.169.10.5997
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发表时间：
2002-11-15
影响因子：
4.4
通讯作者：
Roberts, K
中科院分区：
文献类型：
--
作者：
Jaffar, Z;Wan, KS;Roberts, K
DO11.10 TCR转基因小鼠，我们建立了一个T细胞介导的肺部炎症模型，并证明在吸入OVA后气道中产生高水平的PGI（2）。在体内选择性抑制环氧合酶-2可以特异性地减少PGI（2）的合成，并导致Th 2介导的肺部炎症显著增加，而不是Th 1介导的肺部炎症。由环氧合酶-2抑制剂引起的Th 2介导的炎症反应升高与气道高反应性增强相关，并且与气道中IL-4、IL-5和IL-13水平的显著增加一致，但IL-10产生减少。与这些观察结果一致，我们发现PGI（2）受体的mRNA由Th 2细胞表达，而不是Th 1细胞，并且PGI（2）受体的转录物由IL-4和OVA肽刺激诱导。有趣的是，用PGI（2）或其稳定的类似物carbaprostacyclin处理，增加了Th 2细胞产生IL-10。总的来说，我们的研究结果揭示了PGI（2）在差异性限制Th 2应答中的关键作用，可能是通过促进过敏性肺部炎症部位免疫抑制细胞因子IL-10的产生。这些结果表明炎症过程中产生的前列腺素类在调节粘膜T细胞反应中的重要作用，并突出了过敏性哮喘患者使用环氧合酶-2特异性抑制剂的潜在风险。
DO11.10 TCR transgenic mouse, we developed a model of T cell-mediated pulmonary inflammation and demonstrated that high levels of PGI(2) are produced in the airways following OVA inhalation. Selective inhibition of cyclooxygenase-2 in vivo specifically reduced PGI(2) synthesis and resulted in a marked increase in Th2-mediated, but not Th1-mediated, lung inflammation. The elevated Th2-mediated inflammatory response elicited by the cyclooxygenase-2 inhibitor was associated with enhanced airway hyperreactivity and was coincident with a marked increase in the levels of IL-4, IL-5, and IL-13 in the airways, but a reduction in IL-10 production. In keeping with these observations, we found that the mRNA for the PGI(2) receptor was expressed by Th2, but not Th1, cells, and transcripts for the PGI(2) receptor were induced by IL-4 and OVA peptide stimulation. Interestingly, treatment with PGI(2) or its stable analog, carbaprostacyclin, augmented IL-10 production by Th2 cells. Collectively, our findings reveal a key role for PGI(2) in differentially limiting Th2 responses, possibly by promoting production of the immunosuppressive cytokine IL-10 at the site of allergic lung inflammation. These results indicate an important role for prostanoids generated during inflammation in regulating mucosal T cell responses and highlight a potential risk in the use of cyclooxygenase-2-specific inhibitors by allergic asthmatics.