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001-es BibID:	BIBFORM028538
Első szerző:	Gilad, Eli
Cím:	Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages : role of inhibition of NFkappaB activation / Eli Gilad, Hector R. Wong, Basilia Zingarelli, László Virág, Michael O'Connor, Andrew L. Salzman, Csaba Szabó
Dátum:	1998
ISSN:	0892-6638
Megjegyzések:	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 microM-1 mM, decreased the production of nitrite/nitrate (the breakdown products of NO) as well as the production of 6-keto-prostaglandin F1alpha (the major stable breakdown product of prostacyclin) in macrophages stimulated with bacterial lipopolysaccharide (10 microg/ml). We observed that melatonin reduces iNOS steady-state mRNA levels and iNOS protein expression in the same concentration range (1 microM-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 (NFkappaB). 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 NFkappaB activation. Inhibition of iNOS-derived NO production by melatonin may contribute to the anti-inflammatory effects of this pineal secretory product.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban antioxidants scavengers inflammation gene expression LPS mesangial cells külföldön készült közlemény
Megjelenés:	Faseb Journal 12 : 9 (1998), p. 685-693. -
További szerzők:	Wong, Hector R. Zingarelli, Basilia Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) O'Connor, Michael Salzman, Andrew L. Szabó Csaba (1967-) (orvos)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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