Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon-gamma-treated L929 fibroblasts

V Trajković; V Badovinac; V Janković; T Samardzic; D Maksimović; D Popadić

doi:10.1046/j.1365-3083.1999.00468.x

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Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon-gamma-treated L929 fibroblasts

Journal article

Peer reviewed

Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon-gamma-treated L929 fibroblasts

V Trajković, V Badovinac, V Janković, T Samardzic, D Maksimović and D Popadić

Scandinavian journal of immunology, Vol.49(2), pp.126-130

02/1999

DOI: 10.1046/j.1365-3083.1999.00468.x

PMID: 10075015

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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.

Nitric Oxide - biosynthesis

Cyclosporine - pharmacology

Nitric Oxide Synthase - physiology

L Cells (Cell Line)

Phosphoproteins - genetics

Transcription Factors - genetics

DNA-Binding Proteins - genetics

Enzyme Activation - drug effects

Nitric Oxide Synthase Type II

RNA, Messenger - biosynthesis

Animals

Interferon Regulatory Factor-1

Fibroblasts - drug effects

Tacrolimus - pharmacology

Mice

Immunosuppressive Agents - pharmacology

Interferon-gamma - pharmacology

Fibroblasts - metabolism

Details

Title: Subtitle: Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon-gamma-treated L929 fibroblasts
Creators: V Trajković - Institute for Biological Research, University of Belgrade, Yugoslavia
V Badovinac
V Janković
T Samardzic
D Maksimović
D Popadić
Resource Type: Journal article
Publication Details: Scandinavian journal of immunology, Vol.49(2), pp.126-130
DOI: 10.1046/j.1365-3083.1999.00468.x
PMID: 10075015
NLM abbreviation: Scand J Immunol
ISSN: 0300-9475
eISSN: 1365-3083
Publisher: England
Language: English
Date published: 02/1999
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047620102771

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