Different mechanisms in inhibition of rat macrophage nitric oxide synthase expression by FK 506 and cyclosporin A

Immunopharmacology and Immunotoxicology
Petra StrestíkováHassan Farghali

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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Citations

Jul 19, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Malgorzata ZawadzkaBozena Kaminska
Sep 22, 2006·The British Journal of Ophthalmology·Keiko Oh-iMasahiko Usui
Sep 2, 2010·Journal of Drug Targeting·Norimasa FukataKazuichi Okazaki
Aug 12, 2008·International Immunopharmacology·Mari HämäläinenEeva Moilanen
Mar 19, 2008·Transplant Immunology·Silvana Virginia Gagliotti VigilTânia Silvia Fröde
Jan 24, 2006·International Immunopharmacology·Camila Eduardo MarinhoPaulo Flavio Silveira

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