Association of inducible nitric oxide synthase with asthma severity, total serum immunoglobulin E and blood eosinophil levels

Batra, Jyotsna; Singh, Tejbir; Mabalirajan, Ulanganathan; Sinha, Aditi; Prasad, Rajendra; Ghosh, Balaram

doi:10.1136/thx.2006.057935

Cited by 44 publications

(25 citation statements)

References 33 publications

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“…A few reports show a direct role for iNOS in the process of eosinophil recruitment in that inhibition of iNOS, either pharmacologically or by a gene knockout, reduces airway infiltration by inflammatory cells, especially eosinophils, in models of allergen-induced lung inflammation (reviewed in [25]). Furthermore, two very recent reports showed that polymorphisms in the iNOS gene may be important for asthma protection or susceptibility [11,12]. However, the results of a recent clinical trial conducted by SINGH et al [10] questioned the role of iNOS during asthma and the viability of iNOS as a therapeutic target to treat the symptoms of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…SINGH et al [10] reported that iNOS inhibition with GW274150, a selective and potent iNOS inhibitor, effectively reduces exhaled breath NO but does not affect airway inflammatory cell numbers or airway hyperreactivity after allergen challenge in subjects with asthma. Interestingly, reports by HOLLA et al [11] and BATRA et al [12] show that polymorphisms in the iNOS gene may be important for asthma protection or susceptibility. Such conflicting reports undoubtedly suggest that additional studies are necessary to fully establish the intricate role(s) of NO and its metabolites during airway inflammation.…”

Section: Synthase (Nos): Neuronal Nos (Nnos); Endothelial Nos (Enos);mentioning

confidence: 99%

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Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

Naura

Datta²,

Hans³

et al. 2008

Eur Respir J

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Inducible nitric oxide synthase (iNOS) inhibition was recently shown to exert no effect on allergen challenge in human asthma, raising serious concerns about the role of the protein in the disease. The present study investigated the role of iNOS in ovalbumin-induced eosinophilia from the perspective of its relationship with poly(ADP-ribose) polymerase-1 (PARP-1) and oxidative DNA damage.A mouse model of ovalbumin-induced eosinophilia was used to conduct the studies. iNOS-associated protein nitration and tissue damage were partially responsible for allergeninduced eosinophilia. iNOS expression was required for oxidative DNA damage and PARP-1 activation upon allergen challenge. PARP-1 was required for iNOS expression and protein nitration, and this requirement was connected to nuclear factor-kB. PARP-1 was an important substrate for iNOS-associated by-products after ovalbumin-challenge. PARP-1 nitration blocked its poly(ADPribosyl)ation activity. Interleukin-5 re-establishment in ovalbumin-exposed PARP-1 -/-mice reversed eosinophilia and partial mucus production without a reversal of iNOS expression, concomitant protein nitration or associated DNA damage.The present results demonstrate a reciprocal relationship between inducible nitric oxide synthase and poly(ADP-ribose) polymerase-1 and suggest that expression of inducible nitric oxide synthase may be dispensable for eosinophilia after interleukin-5 production. Inducible nitric oxide synthase may be required for oxidative DNA damage and full manifestation of mucus production. Such dispensability may explain, in part, the reported ineffectiveness of inducible nitric oxide synthase inhibition in preventing allergen-induced inflammation in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Synthase (Nos): Neuronal Nos (Nnos); Endothelial Nos (Enos);mentioning

confidence: 99%

Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

Naura

Datta²,

Hans³

et al. 2008

Eur Respir J

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“…However, the present sample is exclusively of Czech Caucasian origin, restricted to the limited geographical area populated by a quite homogenous population with little admixture. Third, there are certainly other genes and polymorphisms – e.g., of superoxide dismutase, nitric oxide synthase, catalase – that could modulate antioxidant properties and thus are a predisposition to asthma [30,31,32,33,34], which have not been studied in the present case.…”

Section: Discussionmentioning

confidence: 99%

Haplotype Analysis of the NADPH Oxidase p22<sup>phox</sup> Gene in Patients with Bronchial Asthma

Hollá

Kaňková²,

Znojil³

2008

Int Arch Allergy Immunol

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Background: Superoxide produced by airway epithelial and inflammatory cells may contribute to the pathogenesis of asthma. NADPH oxidase (an enzyme complex made up of 5 subunits) is a major source of superoxide in cells. We sought to elucidate the role of genetic variability in the gene encoding the p22^phox subunit of the NADPH oxidase (CYBA, 16q24.3) in asthma susceptibility by means of an association study of haplotypes based on 3 common single nucleotide polymorphisms (SNPs), –930A/G, 242C/T (H72Y) and 640A/G. Methods: SNPs were genotyped by PCR-RFLP methods in a cohort of age- and sex-matched subjects with bronchial asthma (n = 305) and healthy controls (n = 311). Haplotypes were constructed in silico using a Monte Carlo-based algorithm. Furthermore, association of SNPs with sensitization to selected allergens (total 15 tested by skin prick test positivity/negativity) was analyzed. Results: In a single locus analysis, SNPs 242C/T and 640A/G were marginally significantly associated with asthma (p = 0.036 and 0.036, respectively). SNP 640A/G showed a significant association with sensitization to 2 allergens tested (p_corr < 0.02). Haplotype analysis identified a total of 8 haplotypes with population frequencies from 0.07 to 0.22. Distribution of haplotypes significantly differed between cases and controls (omnibus p = 0.017, 10,000 permutations). In the post-hoc analysis, haplotype CYBA₃ (–930G/242T/640A) was associated with an increased risk of asthma (p_corr < 0.05; OR = 1.43, 95% CI 1.06–1.93). Conclusions: This study supports the hypothesis that genetic variability in the CYBA gene probably contributes to the susceptibility to bronchial asthma (or its related phenotypes) in our population.

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“…Therefore, it may be stated that the inhibition of iNOS was due to NILE mediated inhibition of TNF-a. Under the influence of NILE, the decrease in the expression of IL-4 and NO may be beneficial for asthmatic patients, as both IL-4 and iNOS are associated with asthmatic conditions (Batra et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory activity of Nerium indicum through inhibition of nitric oxide and cyclooxygenase activity and modulation of TH1/TH2 cytokine balance in murine splenic lymphocytes

Dey

Chaudhuri

2015

Cytotechnology

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Nerium indicum is a medicinal plant which is used in the treatment of wide range of illness in different ethnopharmacological practices. We have studied the immunomodulatory activity of the 70 % hydro-methanolic extract of N. indicum leaves (NILE) by studying plaque forming cell assay, haemagglutination titre, cell proliferation assay, inhibition of nitric oxide expression and cyclooxygenase activity, estimation of IL-2, IFN-c, IL-4, IL-10, TNF-a and IgM levels. Furthermore, we have characterized NILE with Fourier Transform Infra-red (FTIR) spectroscopy. The results displayed that NILE possessed potent immunomodulatory activity by up-regulating IL-2, IFN-c, IL-10 expression and down-regulating IL-4, TNF-a expression in vitro. NILE also stimulated the in vivo expression of immunoglobulin level in mouse. FTIR analysis revealed phytocompounds of diverse chemical nature present in NILE. Thus, the potent immunomodulatory activity of N. indicum may have serious implications in the treatment of inflammatory diseases in the future.

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Association of inducible nitric oxide synthase with asthma severity, total serum immunoglobulin E and blood eosinophil levels

Cited by 44 publications

References 33 publications

Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

Haplotype Analysis of the NADPH Oxidase p22<sup>phox</sup> Gene in Patients with Bronchial Asthma

Immunomodulatory activity of Nerium indicum through inhibition of nitric oxide and cyclooxygenase activity and modulation of TH1/TH2 cytokine balance in murine splenic lymphocytes

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