The nitrated fatty acid 10-nitro-oleate attenuates allergic airway disease
Abstract
Asthma is a serious, growing problem worldwide. Inhaled steroids, the current standard therapy, are not always effective in this chronic inflammatory disease and can cause adverse effects. We tested the hypothesis that nitrated fatty acids (NFAs) may provide an effective alternative treatment. NFAs are endogenously produced by nonenzymatic reaction of NO with unsaturated fatty acids and exert anti-inflammatory actions both by activating the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)γ and via PPAR-independent mechanisms, but whether they might ameliorate allergic airway disease was previously untested. We found that pulmonary delivery of the NFA 10-nitro-oleic acid (OA-NO2) reduced the severity of murine allergic airway disease, as assessed by various pathological and molecular markers. Fluticasone, an inhaled steroid commonly used to treat asthma, produced similar effects on most end points, but only OA-NO2 induced robust apoptosis of neutrophils and their phagocytosis by alveolar macrophages. This suggests that OA-NO2 may be particularly effective in neutrophil-rich, steroid-resistant severe asthma. In primary human bronchial epithelial cells, OA-NO2 blocked phosphorylation and degradation of IκB and enhanced inhibitory binding of PPARγ to NF-κB. Our results indicate that the NFA OA-NO2 is efficacious in preclinical models of allergic airway disease and may have potential for treating asthma patients.
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NO2-FA display signaling actions that expand both the pharmacokinetics and scope of nitric oxide (·NO) signaling events to include actions beyond the activation of guanylate cyclase-dependent cGMP production.
“NO2-FA display signaling actions that expands both the pharmacokinetics and scope of nitric oxide (·NO) signaling events to include actions beyond the activation of guanylate cyclase-dependent cGMP production [4–7].”
From Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes (2015) · cites this paper as [7]
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- Authors
- Reddy, A. T., Lakshmi, S. P., Dornadula, S., Pinni, S., Rampa, D. R., & Reddy, R. C.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Reddy, Raju C
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-09-01
- Volume
- 191
- Issue
- 5
- Pages
- 2053-2063
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1909650275
- Cited by
- 42
- References
- 48
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 8 · 2018: 6 · 2016: 6 · 2015: 7 · 2014: 3
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-093196, R01HL093196)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- nitrated fatty acids, allergic airway disease, asthma, PPARγ, NF-κB, neutrophil apoptosis, alveolar macrophages, fluticasone, steroid resistance, bronchial epithelial cells, anti-inflammatory therapy
- MeSH terms
- Animals, Anti-Inflammatory Agents, Asthma, Bronchoalveolar Lavage Fluid, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Fatty Acids, Fluorescent Antibody Technique, Humans, Male, Mice, Inbred C57BL, Oleic Acids, Blotting, Western, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, Immunoprecipitation, Mice, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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