Different mechanisms in inhibition of rat macrophage nitric oxide synthase expression by FK 506 and cyclosporin A.
Immunopharmacol Immunotoxicol
; 23(1): 67-74, 2001 Feb.
Article
in En
| MEDLINE
| ID: mdl-11322650
ABSTRACT
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lipopolysaccharides
/
Tacrolimus
/
Cyclosporine
/
Macrophages, Peritoneal
/
Nitric Oxide Synthase
/
Immunosuppressive Agents
Limits:
Animals
Language:
En
Journal:
Immunopharmacol Immunotoxicol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
TOXICOLOGIA
Year:
2001
Document type:
Article
Affiliation country:
Czech Republic