Nuclear Factor-κB — A Pivotal Transcription Factor in Chronic Inflammatory Diseases

Barnes, Peter J.; Karin, Michael

doi:10.1056/nejm199704103361506

Cited by 4,388 publications

(3,031 citation statements)

References 49 publications

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“…It is known that the induction of iNOS is regulated by transcription factors, of which the most important is nuclear factor-kB (NF-kB) [28]. As NF-kB in cells is activated by many factors such as micro-organisms, oxidants, antigens and LPS [29] a possible site of action of oxymetazoline and xylometazoline may be the inhibition of the activation of NF-kB. The nasal mucosa has an important function in preparing the inspired air before entering the lungs through filtering particles and regulating humidity and temperature.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of nitric oxide synthase by nasal decongestants

Westerveld¹,

Voss²,

Hee³

et al. 2000

Eur Respir J

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The nasal decongestants oxymetazoline and xylometazoline are frequently used in the topical treatment of rhinitis and sinusitis. As nitric oxide (NO) is thought to play a role in inflammation of the upper respiratory tract, the aim of this study was to examine the in vitro effects of these compounds on the activity and the expression of NO producing enzymes, including the inducible form of NO synthase (iNOS) and the constitutive isoform of NO synthase (cNOS).Experiments concerning the effects of both compounds on enzymatic activity and enzyme induction of iNOS were performed in a lipopolysaccharide (LPS) induced rat alveolar macrophage cell line (NR8383) using the Griess assay and the 3 H-citrulline assay respectively. The effects on cNOS were examined in fresh rat synaptosomes using the 3 H-citrulline assay. The direct scavenging properties of both compounds were investigated using a amperometric NO sensor.Oxymetazoline and xylometazoline were shown to have a dose dependent inhibitory effect on total iNOS activity indicated by nitrite/nitrate formation in the Griess assay. This effect was found to be due to an inhibition of induction of the enzyme rather than inhibition of the enzyme activity, as was investigated in two separate experiments using the 3 H-citrulline assay. Inhibition of cNOS was moderate and in the same order of magnitude as the inhibition of enzymatic iNOS activity. Direct scavenging of NO could not be detected.As constitutive nitric oxide synthase activity is thought to serve beneficial physiological functions, and exaggerated inducible nitric oxide synthase activity may cause exacerbation of the inflammatory process, pharmacological treatment influencing the nitric oxide generating system should focus on inhibition of inducible nitric oxide synthase alone. The specific characteristics of these decongestants in vitro suggests suitability for this application and may indicate an additional beneficial effect in the treatment of upper respiratory tract inflammation. Eur Respir J 2000; 16: 437±444.

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Section: Discussionmentioning

confidence: 99%

Inhibition of nitric oxide synthase by nasal decongestants

Westerveld¹,

Voss²,

Hee³

et al. 2000

Eur Respir J

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“…The different forms of NF B activate different target genes. 6 Each member of the subunits exhibits a conserved N-terminal region, the Rel-homology domain (RHD) containing the DNA-binding and dimerization domains and the nuclear localization signal (NLS). 7 In unstimulated cells NF B heterodimers are bound to inhibitory proteins (I Bs) masking the NLS in order to prevent translocation from the cytoplasm into the nucleus.…”

Section: Introductionmentioning

confidence: 99%

“…7 In unstimulated cells NF B heterodimers are bound to inhibitory proteins (I Bs) masking the NLS in order to prevent translocation from the cytoplasm into the nucleus. 6 These I B proteins belong to a functionally related family comprising I B␣, I B␤, I B␥, I B⑀, BCL3, p100, p105, IKBL. 8 A common feature of these molecules is the ankyrin repeat of 30-33 amino acids.…”

Section: Introductionmentioning

confidence: 99%

Inhibitors in the NFκB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations

et al. 2002

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“…For example, subacute endothelial activation provides adhesion molecules, cytokines and chemokines. Characteristically, induction of these proteins is regulated by NF B, 8 a factor sensitive to ischemia and reperfusion ex vivo 9 and in vivo. 10 The inhibition of the family of NF Bdependent proinflammatory genes has been found to exert a more substantial cardioprotection after ischemia and reperfusion than antisense ODN directed versus a single proinflammatory gene.…”

Section: By Sonomicrometric Crystals In Infarct Area and Aar Was Assementioning

confidence: 99%

Retroinfusion of NFκB decoy oligonucleotide extends cardioprotection achieved by CD18 inhibition in a preclinical study of myocardial ischemia and retroinfusion in pigs

Kupatt¹,

Wichels²,

Deiss³

et al. 2002

Gene Ther

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Nuclear Factor-κB — A Pivotal Transcription Factor in Chronic Inflammatory Diseases

Cited by 4,388 publications

References 49 publications

Inhibition of nitric oxide synthase by nasal decongestants

Inhibition of nitric oxide synthase by nasal decongestants

Inhibitors in the NFκB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations

Retroinfusion of NFκB decoy oligonucleotide extends cardioprotection achieved by CD18 inhibition in a preclinical study of myocardial ischemia and retroinfusion in pigs

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