COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization
COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization
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DOI：
10.1016/j.jaci.2005.03.042
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发表时间：
2005-08-01
影响因子：
14.2
通讯作者：
Geha, RS
中科院分区：
文献类型：
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作者：
Laouini, D;ElKhal, A;Geha, RS
背景：通过抓挠对皮肤的机械性损伤是特应性皮炎（AD）的重要特征。目的：为探讨环氧合酶2（COX 2）在卵清蛋白致敏诱导的过敏性皮肤炎症中的作用，采用定量PCR和Western blotting方法分别检测考克斯2 mRNA和蛋白的表达。我们在AD小鼠模型中研究了在用卵白蛋白进行EC致敏期间给予考克斯-2选择性抑制剂NS-398的作用，该模型的特征为嗜酸性粒细胞皮肤浸润、总IgE和抗原特异性IgE升高以及对抗原的全身性T（H）2应答。我们进一步研究了考克斯-2缺陷小鼠EC免疫卵清蛋白的反应。结果：胶带剥离引起皮肤考克斯-2 mRNA的短暂增加。相反，卵清蛋白致敏后考克斯-2 mRNA没有增加。在接受NS-398的EC小鼠中，卵清蛋白致敏皮肤部位嗜酸性粒细胞的浸润和IL-4 mRNA的表达、卵清蛋白特异性IgE和IgG（1）抗体反应以及卵清蛋白刺激后脾细胞的IL-4分泌均显着增加。相反，卵清蛋白特异性IgG（2a）。在这些小鼠中，卵清蛋白刺激后脾细胞的抗体应答和IFN-γ分泌显著降低。考克斯-2缺陷小鼠也表现出增强的全身TH 2反应EC sensitivity.Conclusion：这些结果表明，考克斯-2限制TH 2反应EC敏化，并建议考克斯抑制剂可能会更糟。AD患者的过敏性皮肤炎症。
Background: Mechanical injury to the skin by scratching is an important feature of atopic dermatitis (AD). Objective: To investigate the role of COX-2 in allergic skin inflammation elicited by epicutaneous (EC) sensitization via introduction of ovalbumin through shaved tape-stripped skin.Methods: COX-2 mRNA was measured by quantitative PCR, and COX-2 protein was measured by Western blotting. We investigated the effect of administration of the COX-2 selective inhibitor NS-398 during EC sensitization with ovalbumin in a mouse model of AD characterized by eosinophil skin infiltration, elevated total and antigen specific IgE, and a systemic T(H)2 response to antigen. We further examined the response of COX-2-deficient mice to EC immunization with ovalbumin.Results: Tape stripping caused a transient increase in skin COX-2 mRNA. In contrast, COX-2 mRNA was not increased after ovalbumin sensitization. Infiltration by eosinophils and expression of IL-4 mRNA in ovalbumin-sensitized skin sites, ovalbumin specific IgE and IgG(1) antibody responses, and IL-4 secretion by splenocytes after ovalbumin stimulation were all significantly increased in EC mice that received NS-398. In contrast, ovalbumin specific IgG(2a). antibody response and IFN-gamma secretion by splenocytes after ovalbumin stimulation were significantly decreased in these mice. COX-2-deficient mice also exhibited an enhanced systemic TH2 response to EC sensitization.Conclusion: These results demonstrate that COX-2 limits the TH2 response to EC sensitization and suggest that COX inhibitors may worse. allergic skin inflammation in patients with AD.