Regulation of inducible nitric oxide synthase expression by macrophage purinoreceptors and calcium. J Biol Chem 1996 Jan 05;271(1):337-42
Date
01/05/1996Pubmed ID
8550583DOI
10.1074/jbc.271.1.337Scopus ID
2-s2.0-13344284662 (requires institutional sign-in at Scopus site) 156 CitationsAbstract
Macrophage activation is central to the progression of multiple diseases via the release of inflammatory mediators such as cytokines and nitric oxide. Despite the recognized overlap in the regulatory mechanisms involved in mediator production, little formation exists regarding receptor-initiated signaling pathways that coordinately control multiple end points, such as tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production. In this study, the expression of inducible nitric oxide synthase (iNOS) in macrophages is shown to be regulated by calcium and by a purinoreceptor signaling system. The P2Y purinoreceptor partial agonist, 2-methylthio-ATP (2-MeS-ATP), inhibits the expression of iNOS induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) in primary macrophages. Additionally, 2-MeS-ATP attenuates the expression of iNOS in macrophages isolated from CD-1 mice challenged with LPS, and it inhibits LPS-induced TNF-alpha and interleukin-1 alpha (IL-1 alpha) release, thereby preventing endotoxic death. Thus, purinoreceptors and calcium are likely to be critical for macrophage activation and the production of inflammatory mediators stimulated by LPS.
Author List
Denlinger LC, Fisette PL, Garis KA, Kwon G, Vazquez-Torres A, Simon AD, Nguyen B, Proctor RA, Bertics PJ, Corbett JAAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnimals
Calcium
Cell Line
Gene Expression Regulation, Enzymologic
Interferon-gamma
Lipopolysaccharides
Macrophages
Mice
Nitric Oxide Synthase
Receptors, Purinergic
Thionucleotides