In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 69, No. 5 ( 2001-05-01), p. 815-824
Kurzfassung:
Recent studies indicate that nitric oxide (NO) or related compounds mayregulate the production of interleukin (IL)-8, a potent proinflammatorychemokine. Here we report that peroxynitrite (ONOO−)formed by a reaction of NO with superoxide mediates IL-8 geneexpression and IL-8 production in IL-1β- and TNF-α-stimulated humanleukocytes in whole blood. The NO synthase inhibitors aminoguanidineand NG-nitro-l-arginine methylester blocked nuclear accumulation of activator protein-1 (AP-1) andnuclear factor (NF)-κB in both polymorphonuclear (PMN) andmononuclear leukocytes and inhibited IL-8 mRNA expression and IL-8release by ∼90% in response to IL-1β and TNF-α. EnhancedONOO− formation was detected in granulocytes, monocytes, and lymphocytes after challenge with IL-1β or TNF-α. The additionof ONOO− (0.2–80 μM) to whole blood increased nuclearaccumulation of AP-1 and NF-κB in PMN and mononuclear leukocytes andaugmented IL-8 mRNA expression and IL-8 production in aconcentration-dependent fashion. Pyrrolidine dithiocarbamate, aninhibitor of NF-κB activation, attenuated ∼70% of IL-8 releaseevoked by IL-1β, TNF-α, or ONOO−. These resultsindicate that ONOO− formation may underlie the action ofcytokines towards IL-8 gene expression in human leukocytes.
Materialart:
Online-Ressource
ISSN:
0741-5400
,
1938-3673
DOI:
10.1189/jlb.69.5.815
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2001
ZDB Id:
2026833-6
SSG:
12
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