地塞米松和环孢素A对人视网膜色素上皮细胞单核细胞趋化蛋白-1和白细胞介素-8的调节作用

Dexamethasone and cyclosporin A modulation of human retinal pigment epithelial cell monocyte chemotactic protein-1 and interleukin-8.

作者信息

Kurtz R M, Elner V M, Bian Z M, Strieter R M, Kunkel S L, Elner S G

机构信息

Department of Ophthalmology (Kellogg Eye Center), University of Michigan, Ann Arbor 48105, USA.

出版信息

Invest Ophthalmol Vis Sci. 1997 Feb;38(2):436-45.

PMID:9040477

Abstract

PURPOSE

To examine the modulation of interleukin-1 beta (IL-1 beta)- and tumor necrosis factor-alpha (TNF-alpha)-stimulated monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) secretion and transcription in human retinal pigment epithelial (HRPE) cells by dexamethasone (DEX) and cyclosporin A (CSA).

METHODS

Cultured HRPE cells were stimulated with IL-1 beta (0.2 to 20 ng/ml) or TNF-alpha (0.2 to 20 ng/ml) for 8 or 24 hours without (control) and with DEX (10(-8) to 10(-6) M) or with CSA (0.3 to 30 ng/ml). Secreted levels of HRPE MCP-1 and IL-8 were measured in the media using enzyme-linked immunosorbent assay (ELISA). Both MCP-1 and IL-8 mRNA were analyzed by Northern blot.

RESULTS

Although DEX (10(-8) to 10(-6) M) inhibited IL-1 beta-stimulated MCP-1 and IL-8 production, it did not inhibit TNF-alpha-stimulated chemokine secretion. In contrast, CSA significantly inhibited TNF-alpha-stimulated, but not IL-1 beta-stimulated, HRPE MCP-1 and IL-8 secretion. Both DEX and CSA inhibitions showed dose dependence. Northern blot analysis of HRPE steady state MCP-1 and IL-8 mRNA corroborated the ELISA measurements of secreted MCP-1 and IL-8.

CONCLUSIONS

Although DEX and CSA inhibit HRPE MCP-1 and IL-8 secretion, this is dependent on whether the inducing inflammatory mediator is IL-1 beta or TNF-alpha. IL-1 beta-induced chemokine secretion is sensitive to DEX, whereas MCP-1 and IL-8 induced by TNF-alpha are inhibited by CSA. This information may be useful in explaining in vivo observations and in suggesting targeted clinical treatments and combinations of immunosuppressive agents.

摘要

目的

研究地塞米松（DEX）和环孢素A（CSA）对白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）刺激的人视网膜色素上皮（HRPE）细胞中单核细胞趋化蛋白-1（MCP-1）和白细胞介素-8（IL-8）分泌及转录的调节作用。

方法

培养的HRPE细胞分别用IL-1β（0.2至20 ng/ml）或TNF-α（0.2至20 ng/ml）刺激8或24小时，分为不添加（对照）、添加DEX（10⁻⁸至10⁻⁶ M）或添加CSA（0.3至30 ng/ml）的组。使用酶联免疫吸附测定（ELISA）法检测培养基中HRPE细胞分泌的MCP-1和IL-8水平。通过Northern印迹法分析MCP-1和IL-8 mRNA。

结果

虽然DEX（10⁻⁸至10⁻⁶ M）抑制IL-1β刺激的MCP-1和IL-8产生，但不抑制TNF-α刺激的趋化因子分泌。相反，CSA显著抑制TNF-α刺激的HRPE细胞MCP-1和IL-8分泌，但不抑制IL-1β刺激的分泌。DEX和CSA的抑制作用均呈剂量依赖性。HRPE细胞中MCP-1和IL-8 mRNA的Northern印迹分析结果与分泌的MCP-1和IL-8的ELISA检测结果一致。