TY  - JOUR
AU  - Trajković, Vladimir
AU  - Janković, Vladimir
AU  - Badovinac, Vladimir
AU  - Samardžić, Tamara
AU  - Maksimović-Ivanić, Danijela
AU  - Popadić, Dušan
PY  - 1999
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3823
AB  - The effects of immunosuppressant cyclosporin A (CsA) on nitric oxide (NO) production and inducible NO synthase (iNOS) activity in murine L929 fibroblasts were investigated. IFN-gamma-induced NO production in L929 cells was mediated through an iNOS-dependent L-arginine-NO pathway, since it was abrogated by a selective inhibitor of iNOS, aminoguanidine. CsA applied simultaneously with IFN-gamma caused a dose-dependent reduction of NO synthesis in L929 cells. However, CsA did not influence the enzymatic activity of iNOS, since it failed to affect NO production in cells in which iNOS had already been induced with IFN-gamma and any further induction was blocked by the protein-synthesis inhibitor cycloheximide. IFN-gamma-triggered expression of mRNA for interferon regulatory factor-1 was not reduced by CsA-treatment, suggesting that this iNOS transcription factor is not a target in CsA-mediated inhibition of NO synthesis. Finally, FK506 was not able to mimic the inhibitory effect of CsA on NO production in L929 cells, indicating the calcineurin-independent mechanism of CsA action. These results indicate that CsA suppresses NO synthesis in L929 cells independent of calcineurin inhibition, and interfering with intracellular pathways involved in the iNOS induction, rather than inhibiting its enzymatic activity.
PB  - New Jerswy: Wiley-VCH Verlag GmbH & Co
T2  - Scandinavian Journal of Immunology
T1  - Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon-gamma-treated L929 fibroblasts
IS  - 2
VL  - 49
DO  - 10.1046/j.1365-3083.1999.00468.x
SP  - 126
EP  - 130
ER  - 

@article{
author = "Trajković, Vladimir and Janković, Vladimir and Badovinac, Vladimir and Samardžić, Tamara and Maksimović-Ivanić, Danijela and Popadić, Dušan",
year = "1999",
abstract = "The effects of immunosuppressant cyclosporin A (CsA) on nitric oxide (NO) production and inducible NO synthase (iNOS) activity in murine L929 fibroblasts were investigated. IFN-gamma-induced NO production in L929 cells was mediated through an iNOS-dependent L-arginine-NO pathway, since it was abrogated by a selective inhibitor of iNOS, aminoguanidine. CsA applied simultaneously with IFN-gamma caused a dose-dependent reduction of NO synthesis in L929 cells. However, CsA did not influence the enzymatic activity of iNOS, since it failed to affect NO production in cells in which iNOS had already been induced with IFN-gamma and any further induction was blocked by the protein-synthesis inhibitor cycloheximide. IFN-gamma-triggered expression of mRNA for interferon regulatory factor-1 was not reduced by CsA-treatment, suggesting that this iNOS transcription factor is not a target in CsA-mediated inhibition of NO synthesis. Finally, FK506 was not able to mimic the inhibitory effect of CsA on NO production in L929 cells, indicating the calcineurin-independent mechanism of CsA action. These results indicate that CsA suppresses NO synthesis in L929 cells independent of calcineurin inhibition, and interfering with intracellular pathways involved in the iNOS induction, rather than inhibiting its enzymatic activity.",
publisher = "New Jerswy: Wiley-VCH Verlag GmbH & Co",
journal = "Scandinavian Journal of Immunology",
title = "Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon-gamma-treated L929 fibroblasts",
number = "2",
volume = "49",
doi = "10.1046/j.1365-3083.1999.00468.x",
pages = "126-130"
}

Trajković, V., Janković, V., Badovinac, V., Samardžić, T., Maksimović-Ivanić, D.,& Popadić, D.. (1999). Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon-gamma-treated L929 fibroblasts. in Scandinavian Journal of Immunology
New Jerswy: Wiley-VCH Verlag GmbH & Co., 49(2), 126-130.
https://doi.org/10.1046/j.1365-3083.1999.00468.x

Trajković V, Janković V, Badovinac V, Samardžić T, Maksimović-Ivanić D, Popadić D. Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon-gamma-treated L929 fibroblasts. in Scandinavian Journal of Immunology. 1999;49(2):126-130.
doi:10.1046/j.1365-3083.1999.00468.x .

Trajković, Vladimir, Janković, Vladimir, Badovinac, Vladimir, Samardžić, Tamara, Maksimović-Ivanić, Danijela, Popadić, Dušan, "Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon-gamma-treated L929 fibroblasts" in Scandinavian Journal of Immunology, 49, no. 2 (1999):126-130,
https://doi.org/10.1046/j.1365-3083.1999.00468.x . .