Effects of Th2 cytokines on expression of collagen, MMP-1, and TIMP-1 in conjunctival fibroblasts
Effects of Th2 cytokines on expression of collagen, MMP-1, and TIMP-1 in conjunctival fibroblasts
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DOI：
10.1167/iovs.02-0420
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发表时间：
2003-01-01
影响因子：
4.4
通讯作者：
Abatangelo, G
中科院分区：
文献类型：
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作者：
Leonardi, A;Cortivo, R;Abatangelo, G
目的。确定参与慢性过敏性结膜疾病的细胞因子是否可能影响巨乳头的形成和组织重塑。方法。用不同浓度的人重组白细胞介素 (IL)-4、IL-13、干扰素 (IFN)-γ 和肿瘤坏死因子 (TNF)-α 攻击结膜成纤维细胞培养物。测定上清液中原胶原I (PIP)和III (PIIIP)、基质金属蛋白酶(MMP)-1和-9以及金属蛋白酶组织抑制剂(TIMP)-1，并通过RT-PCR评估它们各自的mRNA。结果。与未刺激的细胞相比，IL-4和-13 (10 ng/mL)显着增加了PIP的产生和表达，而IFN-γ在蛋白质和mRNA水平上引起相反的效果。 IL-4和-13均显着降低MMP-1的产生并增加TIMP-1的产生，而TNF-α增加MMP-1和-9的产生。 IL-4 降低了 MMP-1 的表达，而其他测试的细胞因子则增加了 MMP-1 的表达，而所有测试的细胞因子都增加了 TIMP-1 的表达。结论。 IL-4 和-13 增加胶原蛋白的产生并改变MMP-1 及其抑制剂TIMP-1 之间的平衡。这些效应在一定程度上受到 IFN-γ 和 TNF-α 的抑制。
PURPOSE. To determine whether cytokines involved in chronic allergic conjunctival disorders may affect formation of giant papillae and tissue remodeling.METHODS. Conjunctival fibroblast cultures were challenged with different concentrations of human recombinant interleukin (IL)-4, IL-13, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Procollagens I (PIP) and III (PIIIP), matrix metalloproteinase (MMP)-1 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in supernatants, and their respective mRNAs were evaluated by RT-PCR.RESULTS. IL-4 and -13 (10 ng/mL) significantly increased production and expression of PIP compared with nonstimulated cells, whereas IFN-gamma elicited the opposite effect, at both the protein and mRNA levels. Both IL-4 and -13 significantly decreased production of MMP-1 and increased that of TIMP-1, whereas TNF-alpha increased production of MMP-1 and -9. Expression of MMP-1 was reduced by IL-4 and increased by the other tested cytokines, whereas expression of TIMP-1 was increased by all tested cytokines.CONCLUSIONS. IL-4 and -13 increased production of collagen and modified the equilibrium between MMP-1 and its inhibitor, TIMP-1. These effects were partially opposed by IFN-gamma and TNF-alpha.