Inflammatory mediators in uveitis: Differential induction of cytokines and chemokines in Th1-versus Th2-mediated ocular inflammation
Inflammatory mediators in uveitis: Differential induction of cytokines and chemokines in Th1-versus Th2-mediated ocular inflammation
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DOI：
10.4049/jimmunol.168.5.2483
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发表时间：
2002-03-01
影响因子：
4.4
通讯作者：
Gery, I
中科院分区：
文献类型：
--
作者：
Foxman, EF;Zhang, MF;Gery, I
眼部炎症通过沿视轴的脆弱组织的破坏和疤痕导致视力丧失。为了确定参与这一过程的炎症介质，我们使用实时 RT-PCR 来量化 T 细胞介导的眼部炎症过程中某些时间点的 34 种细胞因子、26 种趋化因子和 14 种趋化因子受体的 mRNA 转录本的表达。我们通过将 Ag 特异性 Th1 或 Th2 细胞过继转移到眼睛中表达目标 Ag 的受体中来诱导疾病。我们还将过继转移引起的炎症中观察到的介质表达模式与发生实验性自身免疫性葡萄膜视网膜炎的小鼠眼中观察到的介质表达模式进行了比较。此外，我们使用激光捕获显微切割来检查发炎眼睛中视网膜色素上皮细胞和浸润白细胞产生的趋化因子 mRNA。主要发现如下：1）在过继转移的Th细胞受体中观察到炎症相关分子的三种表达模式：在Th1受体中优先表达，或在Th2受体中优先表达，或在两个受体组中表达相似。 2) 在实验性自身免疫性葡萄膜视网膜炎中，炎症介质的表达模式与 Th1 诱导的疾病中观察到的情况基本相似。 3）在发炎的眼睛中，视网膜色素上皮和浸润白细胞都以不同但重叠的模式表达趋化因子转录本。 4）有趣的是，多种细胞因子、趋化因子和趋化因子受体的转录本在小鼠眼中高水平表达。其中七种分子以前从未与眼睛相关过。这些数据强调了参与眼部炎症发病机制的介质的多样性，并指出上游细胞因子作为潜在的治疗靶点。
Ocular inflammation leads to vision loss through the destruction and scarring of delicate tissues along the visual axis. To identify inflammatory mediators involved in this process, we used real time RT-PCR to quantify the expression of mRNA transcripts of 34 cytokines, 26 chemokines, and 14 chemokine receptors at certain time points during T cell-mediated ocular inflammation. We induced disease by adoptive transfer of Ag-specific Th1 or Th2 cells into recipients expressing the target Ag in their eyes. We also compared the mediator expression patterns seen in adoptive transfer-induced inflammation with that seen in mouse eyes developing experimental autoimmune uveoretinitis. In addition, we used laser capture microdissection to examine chemokine mRNA production by both retinal pigment epithelium cells and infiltrating leukocytes in inflamed eyes. Major findings included the following: 1) Three patterns of expression of the inflammation-related molecules were seen in recipients of adoptively transferred Th cells: preferential expression in Th1 recipients, or in Th2 recipients, or similar expression in both recipient groups. 2) In experimental autoimmune uveoretinitis, the inflammatory mediator expression pattern largely paralleled that seen in Th1-induced disease. 3) Both retinal pigment epithelium and infiltrating leukocytes expressed chemokine transcripts in distinct, but overlapping patterns in inflamed eyes. 4) Interestingly, trancripts of multiple cytokines, chemokines, and chemokine receptors were constitutively expressed in high levels in mouse eyes. Seven of these molecules have not been previously associated with the eye. These data underscore the multiplicity of mediators that participate in the pathogenesis of eye inflammation and point to upstream cytokines as potential therapeutic targets.