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Cell-specific effects of pentoxifylline on nitric oxide production and inducible nitric oxide synthase mRNA expression
Journal article   Open access   Peer reviewed

Cell-specific effects of pentoxifylline on nitric oxide production and inducible nitric oxide synthase mRNA expression

V Trajković, V Badovinac, D Popadić, O Hadzić and M M Stojković
Immunology, Vol.92(3), pp.402-406
11/1997
DOI: 10.1046/j.1365-2567.1997.00354.x
PMCID: PMC1363803
PMID: 9486115
url
https://doi.org/10.1046/j.1365-2567.1997.00354.xView
Published (Version of record) Open Access

Abstract

Cytokine-stimulated astrocytes and macrophages are potent producers of nitric oxide (NO), a free radical proposed to play an important role in organ-specific autoimmunity, including demyelinating diseases of the central nervous system. The aim of this study was to investigate effects of pentoxifylline (PTX), a phosphodiesterase inhibitor with immunomodulatory properties, on NO production and inducible NO synthase (iNOS) mRNA expression in rat astrocytes and macrophages. We have shown that PTX affects cytokine (interferon-gamma, IFN-gamma; interleukin-1, IL-1; tumour-necrosis factor-alpha, TNF-alpha)-induced NO production in both cell types, but in the opposite manner--enhancing in astrocytes and suppressive in macrophages. While PTX did not have any effect on enzymatic activity of iNOS in activated cells, expression of iNOS mRNA was elevated in astrocytes and decreased in macrophages treated with cytokines and PTX. Treatment with PTX alone affected neither NO production nor iNOS mRNA levels in astrocytes or macrophages. This study indicates involvement of different signalling pathways associated with iNOS induction in astrocytes and macrophages, thus emphasizing complexity of regulation of NO synthesis in different cell types.

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