Different mechanisms in inhibition of rat macrophage nitric oxide synthase expression by FK 506 and cyclosporin A
Jazyk angličtina Země Anglie, Velká Británie Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
11322650
DOI
10.1081/iph-100102568
Knihovny.cz E-zdroje
- MeSH
- cyklosporin farmakologie MeSH
- down regulace MeSH
- elektroforéza v agarovém gelu MeSH
- imunosupresiva farmakologie MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- lipopolysacharidy farmakologie MeSH
- messenger RNA metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- peritoneální makrofágy účinky léků enzymologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- potkani Wistar MeSH
- regulace genové exprese enzymů MeSH
- synthasa oxidu dusnatého, typ II MeSH
- synthasa oxidu dusnatého genetika metabolismus MeSH
- takrolimus farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cyklosporin MeSH
- imunosupresiva MeSH
- lipopolysacharidy MeSH
- messenger RNA MeSH
- Nos2 protein, rat MeSH Prohlížeč
- oxid dusnatý MeSH
- synthasa oxidu dusnatého, typ II MeSH
- synthasa oxidu dusnatého MeSH
- takrolimus 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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