Synthesis of prostaglandin H synthase-2 by human alveolar macrophages in response to lipopolysaccharide is inhibited by decreased cell oxidant tone.

Abstract

We previously demonstrated that lipopolysaccharide (LPS) increases expression of the prostaglandin H synthase-2 (PGHS-2) gene (Hempel, S.L., Monick, M.M., and Hunninghake, G.W. (1994) J. Clin. Invest. 93, 391-396). In this study, the expression of the PGHS-2 gene in response to changes in cell oxidant tone was studied. During LPS exposure, inhibition of synthesis of the free radical, NO., resulted in a small decrease in prostaglandin E2 synthesis that did not reach statistical significance. There was no effect on enzyme mass or mRNA. In contrast, incubation of alveolar macrophages in the presence of LPS plus the antioxidant pyrrolidine dithiocarbamate, the spin trap 5,5-dimethyl-1-pyrroline-N-oxide, or hypoxia, resulted in near complete inhibition of prostaglandin E2 synthesis, PGHS-2 enzyme synthesis, and gene transcription of PGHS-2 mRNA. There was no evidence of cytotoxicity. These results demonstrate that synthesis of PGHS-2 in response to LPS is inhibited by agents that decrease cell oxidant tone.

• Authors: S L Hempel, M M Monick, B He, T Yano, G W Hunninghake
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 269 Issue 52 Pg. 32979-84 (Dec 30 1994) ISSN: 0021-9258 [Print] United States
• PMID: 7528741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cyclic N-Oxides
• Lipopolysaccharides
• Oxidants
• RNA, Messenger
• Spin Labels
• Nitric Oxide
• 5,5-dimethyl-1-pyrroline-1-oxide
• Nitric Oxide Synthase
• Prostaglandin-Endoperoxide Synthases
• Amino Acid Oxidoreductases

Topics

• Amino Acid Oxidoreductases (metabolism)
• Cells, Cultured
• Cyclic N-Oxides
• Humans
• Lipopolysaccharides (pharmacology)
• Macrophages, Alveolar (drug effects, enzymology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase
• Oxidants (metabolism)
• Prostaglandin-Endoperoxide Synthases (biosynthesis, genetics)
• RNA, Messenger (metabolism)
• Spin Labels