Dexamethasone and cyclosporin A modulation of human retinal pigment epithelial cell monocyte chemotactic protein-1 and interleukin-8. 1997

R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
Department of Ophthalmology (Kellogg Eye Center), University of Michigan, Ann Arbor 48105, USA.

OBJECTIVE 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.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D010857 Pigment Epithelium of Eye The layer of pigment-containing epithelial cells in the RETINA; the CILIARY BODY; and the IRIS in the eye. Eye Pigment Epithelium
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000893 Anti-Inflammatory Agents Substances that reduce or suppress INFLAMMATION. Anti-Inflammatory Agent,Antiinflammatory Agent,Agents, Anti-Inflammatory,Agents, Antiinflammatory,Anti-Inflammatories,Antiinflammatories,Antiinflammatory Agents,Agent, Anti-Inflammatory,Agent, Antiinflammatory,Agents, Anti Inflammatory,Anti Inflammatories,Anti Inflammatory Agent,Anti Inflammatory Agents
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

Related Publications

R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
August 2006, Life sciences,
R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
January 2006, Ophthalmic research,
R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
October 2018, International ophthalmology,
R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
January 2005, Ophthalmic research,
R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
December 1997, Experimental eye research,
R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
March 2001, Yan ke xue bao = Eye science,
R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
June 1991, Laboratory investigation; a journal of technical methods and pathology,
R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
May 1997, Biochemical Society transactions,
R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
August 2005, Zhonghua yi xue za zhi,
R M Kurtz, and V M Elner, and Z M Bian, and R M Strieter, and S L Kunkel, and S G Elner
October 2005, Human reproduction (Oxford, England),
Copied contents to your clipboard!