FASEB J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gilad, E.
Right arrow Articles by Szabó, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gilad, E.
Right arrow Articles by Szabó, C.
(The FASEB Journal. 1998;12:685-693.)
© 1998 FASEB

RESEARCH COMMUNICATION

Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: role of inhibition of NF{kappa}B activation

Eli Gilada, Hector R. Wonga, Basilia Zingarellia, László Virága, Michael O'Connora, Andrew L. Salzmana, and Csaba Szabóa,1

a Children's Hospital Medical Center, Division of Critical Care, Cincinnati, Ohio 45229, USA

The role of melatonin as an immunomodulator is well established. Recent reports showed that melatonin exerts protective effects in septic and hemorrhagic shock and in inflammation. The expression of the inducible isoform of nitric oxide synthase (iNOS) makes an important contribution to the pathophysiology of shock and inflammation. We studied, in cultured murine macrophages, the role of melatonin in the regulation of the expression of iNOS and defined the mode of melatonin's action. Our results show that melatonin, at 1 µM–1 mM, decreased the production of nitrite/nitrate (the breakdown products of NO) as well as the production of 6-keto-prostaglandin F1{alpha} (the major stable breakdown product of prostacyclin) in macrophages stimulated with bacterial lipopolysaccharide (10 µg/ml). We observed that melatonin reduces iNOS steady-state mRNA levels and iNOS protein expression in the same concentration range (1 µM–1 mM). Melatonin, up to 10 mM, exerted only a slight direct inhibitory effect on iNOS activity. Using iNOS promoter-luciferase constructs, we found that melatonin inhibits iNOS promoter activation. Inhibition of iNOS expression was associated with inhibition of activation of the transcription factor nuclear factor kappa B (NF{kappa}B). We conclude that melatonin inhibits NO production in immunostimulated macrophages mainly by inhibiting the expression of iNOS. This is due to inhibition of iNOS transcription, in part through inhibition of NF{kappa}B activation. Inhibition of iNOS-derived NO production by melatonin may contribute to the anti-inflammatory effects of this pineal secretory product.—Gilad, E., Wong, H. R., Zingarelli, B., Virág, L., O'Connor, M., Salzman, A. L., Szabó, C. Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: role of inhibition of NF{kappa}B activation. FASEB J. 12, 685–693 (1998)


Key Words: inflammation • antioxidants • scavengers • gene expression • LPS • mesangial cells




This article has been cited by other articles:


Home page
 BloodHome page
W.-G. Deng, S.-T. Tang, H.-P. Tseng, and K. K. Wu
Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding
Blood, July 15, 2006; 108(2): 518 - 524.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. Martin, F. Herrera, P. Carrera-Gonzalez, G. Garcia-Santos, I. Antolin, J. Rodriguez-Blanco, and C. Rodriguez
Intracellular Signaling Pathways Involved in the Cell Growth Inhibition of Glioma Cells by Melatonin
Cancer Res., January 15, 2006; 66(2): 1081 - 1088.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
R. J. Reiter and D.-X. Tan
Melatonin: a novel protective agent against oxidative injury of the ischemic/reperfused heart
Cardiovasc Res, April 1, 2003; 58(1): 10 - 19.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
Z. Pei, S. F. Pang, and R. T. F. Cheung
Administration of Melatonin After Onset of Ischemia Reduces the Volume of Cerebral Infarction in a Rat Middle Cerebral Artery Occlusion Stroke Model
Stroke, March 1, 2003; 34(3): 770 - 775.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. Nava, Y. Quiroz, N. Vaziri, and B. Rodriguez-Iturbe
Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats
Am J Physiol Renal Physiol, March 1, 2003; 284(3): F447 - F454.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Y. K. Kim, Y. Y. Jang, E. S. Han, and C. S. Lee
Depressant Effect of Ambroxol on Stimulated Functional Responses and Cell Death in Rat Alveolar Macrophages Exposed to Silica in Vitro
J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 629 - 637.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
R. J. REITER, D. ACUNA-CASTROVIEJO, D.-X. TAN, and S. BURKHARDT
Free Radical-Mediated Molecular Damage: Mechanisms for the Protective Actions of Melatonin in the Central Nervous System
Ann. N.Y. Acad. Sci., June 1, 2001; 939(1): 200 - 215.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
B Zingarelli, Z Yang, P W Hake, A Denenberg, and H R Wong
Absence of endogenous interleukin 10 enhances early stress response during post-ischaemic injury in mice intestine
Gut, May 1, 2001; 48(5): 610 - 622.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
C. HARMS, M. LAUTENSCHLAGER, A. BERGK, D. FREYER, M. WEIH, U. DIRNAGL, J. R. WEBER, and H. HÖRTNAGL
Melatonin is protective in necrotic but not in caspase-dependent, free radical-independent apoptotic neuronal cell death in primary neuronal cultures
FASEB J, September 1, 2000; 14(12): 1814 - 1824.
[Abstract] [Full Text]

Home page
 FASEB J.Home page
E. CRESPO, M. MACÍAS, D. POZO, G. ESCAMES, M. MARTÍN, F. VIVES, J. M. GUERRERO, and D. ACUÑA-CASTROVIEJO
Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats
FASEB J, September 1, 1999; 13(12): 1537 - 1546.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1998 by The Federation of American Societies for Experimental Biology.