PMID: 15240674Jul 9, 2004Paper

Nitric oxide regulates immune cell bioenergetic: a mechanism to understand immunomodulatory functions of nitric oxide-releasing anti-inflammatory drugs

The Journal of Immunology : Official Journal of the American Association of Immunologists
S FiorucciAntonio Morelli

Abstract

The 2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester (NCX-4016) is a NO-releasing derivative of aspirin. In this study, we provide evidence that NCX-4016 delivered to PMBC-derived T lymphocytes and monocytes causes a transitory inhibition of cell respiration and approximately 50% reduction of cellular ATP, which translates in a time-reversible inhibition of cell proliferation and IL-2, IL-4, IL-5, and IFN-gamma secretion. Exposure of lymphocytes and monocytes to aspirin, 2-(acetyloxy)benzoic acid 3-(hydroxymethyl)phenyl ester (NCX-4017), a non-NO-releasing analog of NCX-4016, and cyclooxygenase inhibitors, reduced PG formation, but has no effect on cytokine/chemokine release. In contrast, delivering NO with (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino] diazen-1-ium-1,2 diolate (DETA-NO) reproduced most of the metabolic and anti-cytokine activities of NCX-4016. Scavenging NO with hemoglobin or adding selective substrates of complex II, III, and IV of the mitochondrial respiratory chain reverses NCX-4016' inhibitory activities. Exposure to DETA-NO and NCX-4016 enhances glucose uptake, glycolytic rate, and lactate generation in CD3/CD28-costimulated lymphocytes, while reduced citric acid cycle intermediates. These effec...Continue Reading

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Citations

Aug 15, 2012·Immunological Reviews·Ruoning Wang, Douglas R Green
Feb 4, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Luca SantucciStefano Fiorucci
Dec 13, 2006·Journal of Gastroenterology·Shi-Jun ZhangYan-Li Gu
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kondala R AtkuriLeonore A Herzenberg
May 28, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Weiang YanSanjiv Dhingra
Oct 1, 2009·Shock·Carl F FortinOlivier Lesur
Jul 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bill T AmeredesWilliam J Calhoun
Dec 1, 2020·Journal of Biomolecular Structure & Dynamics·Jan Mohammad Mir, Ram Charitra Maurya
Nov 28, 2021·Journal of Clinical Medicine·Vanessa BianconiMatteo Pirro

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