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J Leukoc Biol. 2000 Mar;67(3):405-14.

Phosphatidylinositol 3-kinase and mTOR mediate lipopolysaccharide-stimulated nitric oxide production in macrophages via interferon-beta.

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1
Department of Biology, San Francisco State University, CA 94132, USA. weinst@sfsu.edu

Abstract

Bacterial lipopolysaccharide (LPS) elicits responses by macrophages that help the body repel infections. Recent evidence indicates that phosphatidylinositol 3-kinase (PI 3-kinase) may mediate some of these responses. Here, we show that exposing macrophages to LPS rapidly increased membrane-associated PI 3-kinase activity and also elevated p70 S6 kinase activity. Inhibitors of PI 3-kinase or the mammalian target of rapamycin (mTOR) fully blocked p70 S6 kinase activation, implying that this kinase is controlled by PI 3-kinase and mTOR. These inhibitors also substantially reduced LPS-induced nitric oxide (NO) production. This inhibition was, in part, attributable to impaired LPS-stimulated secretion of interferon-beta, an autocrine co-factor for NO production. However, the addition of exogenous interferon-beta did not fully restore NO production, indicating that the NO response was being inhibited by another mechanism as well. Together, these data suggest that PI 3-kinase, mTOR, and possibly p70 S6 kinase mediate LPS-induced NO production by regulating the secretion of interferon-beta and by a second undefined mechanism.

PMID:
10733102
DOI:
10.1002/jlb.67.3.405
[Indexed for MEDLINE]

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