iNOS depletion completely diminishes reactive nitrogen-species formation after an allergic response

Koarai, Akira; Ichinose, Masakazu; Sugiura, Hiroaki; Tomaki, Masafumi; Watanabe, Mitsuhiro; Yamagata, Shunsuke; Komaki, Yuichi; Shirato, Kunio; Hattori, Toshio

doi:10.1183/09031936.02.00274902

Cited by 41 publications

(31 citation statements)

References 31 publications

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“…Few inflammatory cells were observed in the lung of PBS-sensitized and challenged control mice. Lungs from OVA-sensitized and challenged mice showed severe inflammation, evidenced by epithelial damage and a large number of inflammatory cells infiltrated around the terminal bronchioles, alveolar sac and peripheral vasculature [17,18]. Luminal narrowing due to the airway wall oedema and luminal obstruction with excess mucus were also observed, which are typical hallmarks of bronchial inflammation.…”

Section: Reduction Of Oxidative Stress By Hpox Nanoparticles In the Pmentioning

confidence: 97%

Reduction of oxidative stress by p-hydroxybenzyl alcohol-containing biodegradable polyoxalate nanoparticulate antioxidant

et al. 2011

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Section: Reduction Of Oxidative Stress By Hpox Nanoparticles In the Pmentioning

confidence: 97%

Reduction of oxidative stress by p-hydroxybenzyl alcohol-containing biodegradable polyoxalate nanoparticulate antioxidant

et al. 2011

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“…Murine models have confirmed that iNOS expression is increased in airways following antigen challenge (28). To determine whether the increased inflammation observed following ADMA infusion was associated with altered iNOS expression in the airways, we visualized iNOS expression in lungs using immunohistochemistry (IHC) (Fig.…”

Section: Effect Of Elevated Adma On Inos Expression In Airway Epithelmentioning

confidence: 99%

“…Although it is known that NO plays a role in asthma by contributing to pulmonary inflammation after allergen challenge (49,69), the contribution of each of the NOS isoforms to inflammation in the airway is unclear. Pharmacological inhibitors of NOS have been used to study the role of specific NOS isoforms in asthma and have provided support for iNOSmediated NO production in the potentiation of airway inflammation (28,52). In contrast, overexpression of eNOS attenuates airway inflammation in a murine model of allergic asthma (60) indicating a delicate balance between NO production from constitutive NOS isoforms and that produced by iNOS.…”

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confidence: 99%

Asymmetric dimethylarginine potentiates lung inflammation in a mouse model of allergic asthma

Klein

Weigel

Buford

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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(NOS), is an important mediator of lung inflammation in allergic asthma. Asymmetric dimethylarginine (ADMA), a competitive endogenous inhibitor of NOS, is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Elevated ADMA has been shown to affect lung function in mice, and by inhibiting NOS it alters NO and reactive oxygen species production in mouse lung epithelial cells. However, the effects of altered ADMA levels during lung inflammation have not been explored. A model of allergen-induced airway inflammation was utilized in combination with the modulation of endogenous circulating ADMA levels in mice. Airway inflammation was assessed by quantifying inflammatory cell infiltrates in lung lavage and by histology. Lung DDAH expression was assessed by quantitative PCR and immunohistochemistry. Nitrite levels were determined in lung lavage fluid as a measure of NO production. iNOS expression was determined by immunohistochemistry, immunofluorescence, Western blot, and quantitative PCR. NF-B binding activity was assessed by a transcription factor binding assay. Allergen-induced lung inflammation was potentiated in mice with elevated circulating ADMA and was reduced in mice overexpressing DDAH. Elevated ADMA reduced nitrite levels in lung lavage fluid in both allergenchallenged and control animals. ADMA increased iNOS expression in airway epithelial cells in vivo following allergen challenge and in vitro in stimulated mouse lung epithelial cells. ADMA also increased NF-B binding activity in airway epithelial cells in vitro. These data support that ADMA may play a role in inflammatory airway diseases such as asthma through modulation of iNOS expression in lung epithelial cells. airway; dimethylarginine dimethylaminohydrolase; inducible nitric oxide synthase ONE OF THE KEY PATHOGENIC features of asthma is the infiltration and activation of inflammatory cells in the airways (6,17,21,22). Lung inflammation in allergic asthma is induced by a cascade of reactions involving several mediators including nitric oxide (NO) (55). NO is a highly reactive radical formed by the metabolism of the semi-essential amino acid L-arginine by nitric oxide synthase (NOS) (29). There are three predominant NOS isoforms. The constitutive isoforms of NOS (cNOS) are expressed mainly in nonadrenergic noncholinergic nerves (nNOS), in endothelial cells (eNOS), and in airway epithelium (nNOS and eNOS) (2,19,29,62), and are involved in the physiological regulation of the airway by local production of small amounts of NO. The third isoform (iNOS) is induced following exposure to proinflammatory cytokines and is expressed in epithelial and inflammatory cells of the airway (57). Although it is known that NO plays a role in asthma by contributing to pulmonary inflammation after allergen challenge (49, 69), the contribution of each of the NOS isoforms to inflammation in the airway is unclear. Pharmacological inhibitors of NOS have been used to study the role of specific NOS isoforms in asthma and have provided support for iNOSmediate...

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“…The literature shows that asthmatic airway hyperreactivity has to do with increased expression of iNOS (Koarai et al 2002;Schuiling et al 1998), which suggests that this isoform is involved in the pathogenesis AHR and asthma. We confirmed the role of iNOS in the present study, finding that after L-NAME pretreatment in healthy animals its expression was very low, but it dramatically increased after allergen exposition.…”

Section: Discussionmentioning

confidence: 98%

The Influence of L-NAME on iNOS Expression and Markers of Oxidative Stress in Allergen-Induced Airway Hyperreactivity

Antošová

Strapková

Mikolka

et al. 2014

Advances in Experimental Medicine and Biology

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Nitric oxide (NO) effects in airways are influenced by the activity of NO-synthase isoforms and NO metabolism. Inducible NO-synthase (iNOS), which produces large amounts of NO, is active during the inflammatory process. NO quickly reacts, producing reactive oxygen species (ROS). In this study we attempted to detect the expression of iNOS and markers of ROS in the airway hyperreactivity (AHR) condition. The study was performed in guinea pigs, divided into four groups. Two groups were treated with the non-selective inhibitor of NO-synthase L-NAME. The other two groups were used as controls. Exhaled NO was monitored in vivo, AHR was assessed both in vivo and in vitro, and the expression of iNOS in lung homogenate, and oxidative stress markers were measured in the venous blood. L-NAME significantly affected the AHR only in in vitro condition, blocked the expression of iNOS in control but not in sensitized animals, and decreased the level of exhaled NO. The results concerning the oxidative stress markers are equivocal. The study confirmed that NO is involved in the regulation of AHR; the effects being mediated via iNOS and ROS activity.

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iNOS depletion completely diminishes reactive nitrogen-species formation after an allergic response

Cited by 41 publications

References 31 publications

Reduction of oxidative stress by p-hydroxybenzyl alcohol-containing biodegradable polyoxalate nanoparticulate antioxidant

Reduction of oxidative stress by p-hydroxybenzyl alcohol-containing biodegradable polyoxalate nanoparticulate antioxidant

Asymmetric dimethylarginine potentiates lung inflammation in a mouse model of allergic asthma

The Influence of L-NAME on iNOS Expression and Markers of Oxidative Stress in Allergen-Induced Airway Hyperreactivity

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