Platelet activating factor (PAF) antagonists on cytokine induction of iNOSand sPLA(2) in immortalized astrocytes (DITNC)

Authors
Citation
Jh. Wang et Gy. Sun, Platelet activating factor (PAF) antagonists on cytokine induction of iNOSand sPLA(2) in immortalized astrocytes (DITNC), NEUROCHEM R, 25(5), 2000, pp. 613-619
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROCHEMICAL RESEARCH
ISSN journal
0364-3190 → ACNP
Volume
25
Issue
5
Year of publication
2000
Pages
613 - 619
Database
ISI
SICI code
0364-3190(200005)25:5<613:PAF(AO>2.0.ZU;2-T
Abstract
Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocho line) and its receptor are known to play important roles in modulating neur onal plasticity and inflammatory responses, particularly during neuronal in jury. PAF receptors are widespread in different brain regions and are prese nt on the cell surface as well as in intracellular membrane compartments. A strocytes are immune active cells and are responsive to cytokines, which st imulate signaling cascades leading to transcriptional activation of genes a nd protein synthesis. Our recent studies indicate the ability of cytokines, e.g., tumor necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 be ta) and interferon-gamma (IFN gamma), to induce the inducible nitric oxide (iNOS) and secretory phospholipase A(2) (sPLA(2)) genes in immortalized ast rocytes (DITNC) (Li et al., J. Interferon and Cytokine Res. 19: 121-127. 19 99). The main objective for this study is to examine the effects of PAF ant agonists on cytokine induction of iNOS and sPLA(2) in these cells. Results show that BN50730, a synthetic PAF antagonist, but not BN52021, a natural P AF antagonist (ginkolide B) can dose-dependently inhibit cytokine induction of NO production and sPLA(2) release. Inhibition of NO production by BN507 30 corroborated well with the decrease in iNOS protein and mRNA levels as w ell as binding of NF-kappa B and STAT-1 to DNA, suggesting that BN50730 act ion is upstream of the transcriptional process. These results are in agreem ent with the role of intracellular PAF in regulating the cytokine signaling cascade in astrocytes and further suggest the possible use of BN50730 as a therapeutic agent for suppressing the inflammatory pathways elicited by cy tokines.