Functional assay of NF-κB translocation into nuclei by laser scanning cytometry: inhibitory effect by dexamethasone or theophylline

Tomita, Katsuyuki; Chikumi, Hiroki; Tokuyasu, Hirokazu; Yajima, Hiroki; Hitsuda, Yutaka; Matsumoto, Yukio; Sasaki, Takeshi

doi:10.1007/pl00005349

Cited by 38 publications

(25 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…by counteracting the penile fibrotic process in a rat model of Peyronie' s disease (21). Therefore, there is a possibility that some PDE inhibition-unrelated features of certain drugs or drug families might contribute to their effect on iNOS-mediated NO synthesis (23); this indeed could be the case with methylxanthines and their derivatives, the antioxidant activity of which might be partly responsible for their blocking of redox-sensitive activation of iNOS transcription factor NF-kB (25). Methylxanthine derivative pentoxifylline is a non specific cAMP-PDE inhibitor used for a wide variety of inflammatory and fibrotic conditions.…”

Section: Treatmentmentioning

confidence: 99%

Peyronie’s disease: A “triple oxygenant therapy”

Ciociola

Colpi

2013

Arch Ital Urol Androl

View full text Add to dashboard Cite

Objectives: To evaluate the effects of upregulators of nitric oxide in one patient with Peyronie's disease, after non significant improvement following intracavernosal verapamil. Methods: A 20-years-old Caucasian male presented with penile induration in flaccid state, persistent during erection and associated with mild pain at third middle of penis. After treatment with intracavernosal verapamil for 4 months with relief of penile discomfort, followed by counseling on the use of penile extender for at least 6 hours per day, he was prescribed pentoxifylline associated with tadalafil plus levo-arginine, propionil-carnitine and Vitamin B3. Results: After almost 2 years, the septal thickness was reduced at ultrasound evaluation after this "triple oxygenant therapy". Conclusion: NO-iNOS biology in Peyronie patients is the very protagonist in modulating penile fibrosis through up-regulation of NO-cGMP pathway that influences penile health by preventing and reversing fibrosis in the tunical albuginea.

show abstract

Section: Treatmentmentioning

confidence: 99%

Peyronie’s disease: A “triple oxygenant therapy”

Ciociola

Colpi

2013

Arch Ital Urol Androl

View full text Add to dashboard Cite

show abstract

“…It has been shown that no longer than 24 h is needed for inhibition of iNOS activity (24 h) [75] and only 30 min for the NF-kB after application of corticosteroids [77].…”

Section: Inhaled Corticosteroidsmentioning

confidence: 99%

“…The short-acting b 2 -agonist salbutamol (5 mg via nebulizer or 400 mg by metered-dose inhaler) has no acute effect on exhaled NO [9,10,77]. Similarly, 1 week of treatment with a long-acting inhaled b 2 -agonists, salmeterol, does not reduce NO in adults or children [9±11].…”

Section: Inhaled B 2 -Agonistsmentioning

confidence: 99%

Clinical aspects of exhaled nitric oxide

2000

View full text Add to dashboard Cite

There has been intense research into the role nitric oxide (NO) plays in physiological and pathological mechanisms and its clinical significance in respiratory medicine.Elevated levels of exhaled levels of exhaled NO in asthma and other inflammatory lung diseases lead to many studies examining NO as potential markers of airway inflammation, enabling repeated noninvasive and standardized monitoring of airway inflammation. In airway inflammation, NO is not merely a marker but may have antiinflammatory and pro-inflammatory effects. Significant correlation has been found between exhaled NO and skin test scores in steroid naive asthmatic patients, allowing to discriminate patients with and without airway responsiveness. Exhaled NO is significantly elevated in acute asthma, or steroid-resistant severe asthma, or when the maintenance dose of inhaled steroids is reduced, and quickly reduced down to the levels in patients with stable asthma after steroid treatment. Exhaled NO has been successfully used to monitor anti-inflammatory treatment with inhaled corticosteroids in asthma. Exhaled NO is extremely sensitive and rapid marker of the dose-dependent effect of steroid treatment, or asthma deterioration, which is increased to any changes in lung function, provocative concentration causing a 20% fall in forced expiratory volume, sputum eosinophilia or asthma symptoms. Exhaled NO is not increased in stable chronic obstructive pulmonary disease (COPD), but patients with unstable COPD, or bronchiectasis have high NO levels. Exhaled and nasal NO are diagnostically low in cystic fibrosis and primary pulmonary dyskinesia.Analysis of exhaled air, including nitric oxide, is feasible and could provide a noninvasive method for use in monitoring and management of lung diseases. Eur Respir J 2000; 16: 781±792.

show abstract

“…Relatively recently, a correlation of note was observed between the suppression of proinflammatory cytokine production and the inhibition of NF-B/NFAT signaling pathway mediated by PDE type 4 isozymes (Navarro et al, 1998). Moreover, Tomita et al (1999) reported a novel role for dexamethasone and theophylline, another nonspecific inhibitor of PDE, in regulating NF-B translocation/activation and cytokine expression. In addition, selective inhibition of PDE 3 attenuated the activation of NF-B and subsequently blockaded the downstream cytokine signaling pathway (Matsumori et al, 2000).…”

mentioning

confidence: 99%

Immunopharmacological Potential of Selective Phosphodiesterase Inhibition. II. Evidence for the Involvement of an Inhibitory-κB/Nuclear Factor-κB-Sensitive Pathway in Alveolar Epithelial Cells

Haddad¹,

Land²,

Tarnow‐Mordi³

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

In this report we investigated the immunopharmacological role of selective and nonselective phosphodiesterase (PDE) inhibition in regulating the inhibitory-B (IB-␣)/nuclear factor-B (NF-B) signaling transduction pathway. In fetal alveolar type II epithelial cells, PDE blockade at the level of the diverging cAMP/cGMP pathways differentially regulated the phosphorylation and degradation of IB-␣, the major cytosolic inhibitor of NF-B. Whereas selective inhibition of PDEs 1, 3, and 4, by the action of 8-methoxymethyl-3-isobutyl-1-methylxanthine, amrinone, and rolipram, respectively, exhibited a tendency to augment the translocation of NF-B 1 (p50), RelA (p65), RelB (p68), and c-Rel (p75), selective blockade of PDE 5, 6, and 9, by the action of 4-{[3Ј,4Ј-(methylenedioxy)benzyl]amino}-6-methoxyquinazoline and zaprinast, attenuated lipopolysaccharide-endotoxin (LPS)-mediated NF-B translocation. Pentoxifylline, a nonspecific PDE inhibitor, reversed the excitatory effect of LPS on NF-B subunit nuclear localization, in a dosedependent manner. Furthermore, analysis of NF-B activation under the same conditions revealed a biphasic effect mediated by LPS. PDEs 1, 3, and 4 inhibition was associated with upregulating NF-B transcriptional activity. In contrast, blockading the activity of PDEs 5, 6, and 9 negatively attenuated LPS-mediated NF-B activation, similar to the effect of 3,7-dihydro-3,7-dimethyl-1-(5-oxohexyl)-1H-purine-2,6-dione (pentoxifylline). These results indicate that selective and nonselective interference with the control of the dynamic equilibrium of cyclic nucleotides via PDE isoenzyme regulation represents an immunoregulatory mechanism that requires the differential, biphasic targeting of the IB-␣/NF-B pathway.Although the transcription factor nuclear factor-B (NF-B) has been originally recognized in regulating gene expression in B-cell lymphocytes (Sen and Baltimore, 1986), subsequent investigations have demonstrated that it is one member of a ubiquitously expressed family of Rel-related transcription factors that serve as critical regulators of many genes, including those of proinflammatory cytokines (Siebenlist et al

show abstract

Functional assay of NF-κB translocation into nuclei by laser scanning cytometry: inhibitory effect by dexamethasone or theophylline

Cited by 38 publications

References 33 publications

Peyronie’s disease: A “triple oxygenant therapy”

Peyronie’s disease: A “triple oxygenant therapy”

Clinical aspects of exhaled nitric oxide

Immunopharmacological Potential of Selective Phosphodiesterase Inhibition. II. Evidence for the Involvement of an Inhibitory-κB/Nuclear Factor-κB-Sensitive Pathway in Alveolar Epithelial Cells

Contact Info

Product

Resources

About