Different mechanisms in inhibition of rat macrophage nitric oxide synthase expression by FK 506 and cyclosporin A
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
11322650
DOI
10.1081/iph-100102568
Knihovny.cz E-resources
- MeSH
- Cyclosporine pharmacology MeSH
- Down-Regulation MeSH
- Electrophoresis, Agar Gel MeSH
- Immunosuppressive Agents pharmacology MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Lipopolysaccharides pharmacology MeSH
- RNA, Messenger metabolism MeSH
- Nitric Oxide metabolism MeSH
- Macrophages, Peritoneal drug effects enzymology MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Rats, Wistar MeSH
- Gene Expression Regulation, Enzymologic MeSH
- Nitric Oxide Synthase Type II MeSH
- Nitric Oxide Synthase genetics metabolism MeSH
- Tacrolimus pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cyclosporine MeSH
- Immunosuppressive Agents MeSH
- Lipopolysaccharides MeSH
- RNA, Messenger MeSH
- Nos2 protein, rat MeSH Browser
- Nitric Oxide MeSH
- Nitric Oxide Synthase Type II MeSH
- Nitric Oxide Synthase MeSH
- Tacrolimus MeSH
The modulatory effect of FK 506 and cyclosporin A (CsA) on the expression of inducible nitric oxide synthase (iNOS) in macrophages and mechanisms of their action were analysed. Isolated rat peritoneal macrophages were cultured for 12 or 24 h with or without lipopolysaccharide (LPS) (5 microg/ml) and in the absence or presence of FK 506 or CsA (0.1 and 1 microg/ml). Total RNA from macrophages was isolated and the expression of the gene for iNOS was assessed by using RT-PCR. The concentration of NO2- in culture supernatants was taken as a measure of nitric oxide (NO) production. FK 506 (0.1 and 1 microg/ml) reduced the LPS-induced increase of NO2- levels by 68% and 81%, respectively. CsA (0.1 and 1 microg/ml) decreased levels of nitrites by 39% and 69%, respectively. The results obtained suggest that both immunosuppressive drugs exhibit dose-dependent inhibitory effect on NO production and that FK 506 is more potent agent than CsA, in this respect. FK 506 exhibits its inhibitory effect on a phosphatase at the transcriptional level in macrophages. iNOS expression down-regulation by CsA is occurred post-transcriptionally.
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