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Cytokine‐ and Endotoxin‐Induced Nitric Oxide Synthase in Rat Astroglial Cultures: Differential Modulation by Angiotensin II
Author(s) -
Kopnisky Kathy L.,
Sumners Colin,
Chandler L. Judson
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68030935.x
Subject(s) - nitric oxide synthase , lipopolysaccharide , nitric oxide , cytokine , endocrinology , tumor necrosis factor alpha , angiotensin ii , medicine , stimulation , chemistry , immune system , biology , immunology , blood pressure
Recent studies have shown that the stimulatory effects of bacterial endotoxin [lipopolysaccharide (LPS)] on inducible nitric oxide (NO) synthase (iNOS) in astroglia are significantly reduced by the peptide angiotensin II (Ang II). In the present study we have compared the modulatory actions of Ang II on cytokine‐ and LPS‐stimulated iNOS in astroglia cultured from adult rat brain. Incubation of astroglia with LPS (100 ng/ml; 24 h) and/or combinations of interleukin‐1β (IL‐1β; 10 ng/ml, 24 h), interferon‐γ (IFN‐γ; 100 U/ml, 24 h), or tumor necrosis factor‐α (TNF‐α; 100 ng/ml, 24 h) resulted in significant increases of iNOS mRNA, iNOS protein, and NO production, with the latter indicated by increased nitrite accumulation. The effects of LPS, IL‐1β, and TNF‐α were significantly decreased by coincubation with Ang II (100 ng/ml, 24 h). In contrast, Ang II did not alter the stimulation of iNOS mRNA levels and NO production elicited by IFN‐γ. Therefore, Ang II differentially modulates the stimulatory actions of LPS and cytokines on iNOS, and subsequently NO production, in astroglia. These data suggest that Ang II may have an important modulatory role in intracerebral immune responses that involve production of NO by astroglia.