Nitric oxide, peroxynitrite, and lower respiratory tract inflammation

Robbins, Richard; Hadeli, Khaled; Nelson, Dan K.; Sato, Etsuro; Hoyt, Jeffrey C.

doi:10.1016/s0162-3109(00)00220-4

Cited by 23 publications

(21 citation statements)

References 25 publications

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“…26 The main site of inducible (type II) NO synthase expression is the airway epithelium, and it is also observed in several inflammatory cells. 27 It is therefore conceivable that epithelial cells of small airways and inflammatory cells infiltrating peripheral airways wall contribute to the levels of NO measured in expired air. Chronic inflammation can be associated with modified structure of the small airway walls, which contributes to the nonhomogeneous obstruction of small airways.…”

Section: Discussionmentioning

confidence: 99%

Small airways function and molecular markers in exhaled air in mild asthma

Battaglia

Hertog²,

Timmers

et al. 2005

Thorax

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Background: Several studies suggest that the periphery of the lung is the major site of inflammation in asthma. Fractional exhaled nitric oxide (FeNO) and 8-isoprostane have been proposed as biomarkers of inflammation and oxidative stress. We therefore hypothesised that small airway dysfunction in asthma is of inflammatory origin that can be detected by molecular markers in exhaled air. To test this hypothesis, we examined the relationship of FeNO and 8-isoprostane in exhaled air with small airways function as assessed by the single breath nitrogen test. Methods: Sixteen patients (14 women) with mild atopic asthma (forced expiratory volume in 1 second .80% predicted) of mean (SD) age 23.0 (5.5) years participated in a cross sectional study. FeNO was recorded by chemiluminescence and 8-isoprostane was measured by ELISA in concentrated exhaled breath condensate. The slope of phase III (dN 2 ) and the closing volume (CV) were assessed from the single breath washout curve. Results: The median FeNO level was 30.4 ppb (range 10.1-82.8), the median 8-isoprostane concentration in exhaled breath condensate was 2.2 pg/ml (range 1.6-2.7), and the mean (SD) dN 2 value was 1.1 (0.4)% N 2 /l. FeNO was positively associated with dN 2 (r s = 0.54, p = 0.032) while 8-isoprostane was inversely correlated with FEV 1 % predicted (r s = 20.58; p = 0.017) and CV as a percentage of vital capacity (r s = 0.58; p = 0.019). Conclusions: FeNO and 8-isoprostane in exhaled air are associated with small airways function in mild asthma. This suggests that these markers reflect small airway inflammation and favours a role for them as disease markers that is complementary to spirometry in the monitoring of patients with asthma.

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Section: Discussionmentioning

confidence: 99%

Small airways function and molecular markers in exhaled air in mild asthma

Battaglia

Hertog²,

Timmers

et al. 2005

Thorax

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“…One marker of inflammation has been measurement of NO, a gas produced by lung epithelial cells, which has been shown to be elevated in several inflammatory airway conditions (6). We hypothesized that doxycycline possesses potent anti-inflammatory properties in murine lung epithelial cells, leading to a reduction of NO produced by inducible NO synthase (iNOS) 3 and that this inhibition is due, at least in part, to decreased stabilization and expression of iNOS mRNA and its translation to form active iNOS enzyme.…”

mentioning

confidence: 99%

Doxycycline Modulates Nitric Oxide Production in Murine Lung Epithelial Cells

Hoyt

Ballering

Numanami

et al. 2006

The Journal of Immunology

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Many effective therapeutic agents exhibit effects that are different from their intended primary mode of action. Antibiotics such as doxycycline and erythromycin A are no exception. They also display anti-inflammatory activity. Using LA4 murine lung alveolar epithelial cells, effects of doxycycline and erythromycin A on inducible NO synthase (iNOS) NO production as well as iNOS protein and mRNA production were investigated. Induction of iNOS was accomplished by treatment with cytomix (TNF-α, IL-1β, and IFN-γ each at 5 ng/ml). Production of NO or iNOS was not detected in controls with or without erythromycin A. In the presence of cytomix, erythromycin A did not decrease NO, nitrite, iNOS protein, or mRNA production. In contrast, doxycycline caused a dose-dependent decrease in NO, nitrite, iNOS protein, and mRNA production in cytomix-treated cells. Doxycycline at 30 μg/ml produced a 90% decrease in nitrite and NO production and a 52% decrease in iNOS mRNA transcription compared with cytomix treatment alone. Actinomycin D treatment suggests that doxycycline decreases stability of iNOS mRNA in cytomix-treated cells. To determine a mechanism for the decrease in iNOS expression, NF-κB and AP-1 transcription regulatory systems and p38 MAPK were examined. Doxycycline treatment gave no statistically significant change in NF-κB activation but did decrease p38 MAPK protein in cytomix-treated cells by 50%, suggesting that p38 MAPK may be responsible for stabilization of iNOS mRNA. These results demonstrate that doxycycline decreases NO production from iNOS by destabilization of iNOS mRNA via decreased expression of p38 MAPK.

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“…This nitrosative stress can thus alter protein function. 84 Production of NOx therefore increases during inflammation and oxidative stress, but can vary depending on pulmonary damage, medication 85 and smoking status. 86 Even though the data in the literature are contradictory, the simplicity of Griess colorimetry assay combined with its low cost favors analysis of these biomarkers.…”

Section: Nitrogen Oxidesmentioning

confidence: 99%