Dexamethasone and cyclosporin A modulation of human retinal pigment epithelial cell monocyte chemotactic protein-1 and interleukin-8
| Autor: | R M, Kurtz, V M, Elner, Z M, Bian, R M, Strieter, S L, Kunkel, S G, Elner |
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| Rok vydání: | 1997 |
| Předmět: |
Dose-Response Relationship
Drug Tumor Necrosis Factor-alpha Interleukin-8 Anti-Inflammatory Agents Enzyme-Linked Immunosorbent Assay Blotting Northern Dexamethasone Cyclosporine Humans RNA Messenger DNA Probes Pigment Epithelium of Eye Cells Cultured Chemokine CCL2 Immunosuppressive Agents Interleukin-1 |
| Zdroj: | Investigative ophthalmologyvisual science. 38(2) |
| ISSN: | 0146-0404 |
| Popis: | 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).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.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.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. |
| Databáze: | OpenAIRE |
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