Mechanisms underlying cigarette smoke-induced NF-kappaB activation in human lymphocytes: the role of reactive nitrogen species

Cigarette smoke (CS) is an important source of reactive nitrogen species (RNS). It has been demonstrated that CS constitutes the highest source of exogenous nitric oxide and peroxynitrite to which humans are exposed. NF-kappaB is a key inflammatory, redox-sensitive transcription factor, which role i...

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Published in:Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2007-11, Vol.58 Suppl 5 (Pt 1), p.275
Main Authors: Hasnis, E, Bar-Shai, M, Burbea, Z, Reznick, A Z
Format: Article
Language:English
Subjects:
Adult
Cells, Cultured
Dose-Response Relationship, Drug
Enzyme Activation
Enzyme Induction
Glutathione - metabolism
Humans
I-kappa B Kinase - metabolism
I-kappa B Proteins - metabolism
Lymphocytes - drug effects
Lymphocytes - enzymology
Lymphocytes - metabolism
Middle Aged
NF-kappa B - metabolism
NF-KappaB Inhibitor alpha
Nicotiana
Nitric Oxide - metabolism
Nitric Oxide Synthase Type II - biosynthesis
Oxidative Stress - drug effects
Peroxynitrous Acid - metabolism
Phosphorylation
Protein Processing, Post-Translational
Reactive Nitrogen Species - metabolism
Smoke - adverse effects
Smoking - metabolism
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Summary:Cigarette smoke (CS) is an important source of reactive nitrogen species (RNS). It has been demonstrated that CS constitutes the highest source of exogenous nitric oxide and peroxynitrite to which humans are exposed. NF-kappaB is a key inflammatory, redox-sensitive transcription factor, which role in CS-induced airway inflammation is unclear. Moreover, the role of RNS in the activation of NF-kappaB and in inflammation has remained vague. This study investigated CS-induced NF-kappaB activation in human lymphocytes and assessed the involvement of CS-derived RNS in NF-kappaB activation and their possible biological effects. Mild, but not high, exposure to CS induced NF-kappaB in lymphocytes through IKK activation, I-kappaBalpha degradation, and the reduction in the intracellular glutathione levels. Peroxynitrite, but not NO, mimicked the effects of CS on NF-kappaB. Reduction of intracellular peroxynitrite formation by the inhibition of the mitochondrial respiratory chain resulted in decreased activation of NF-kappaB by CS. NF-kappaB-induced iNOS levels were increased in response to CS. Low levels of CS exposure induced classical NF-kappaB activation pathway in lymphocytes via intracellular formation of peroxynitrite, through a reaction between smoke-derived NO and endogenously produced superoxide. This NF-kappaB activation resulted in inflammatory gene expression, which may contribute to CS-related airway inflammation.
ISSN:0867-5910