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Suppressing Allergic Airway Disease with Nitrated Fatty Acids
Author(s) -
Reddy Aravind T,
Lakshmi Sowmya P,
Dornadula Sireesh,
Pinni Sudheer,
Rampa Dileep R,
Reddy Raju C
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1216.3
Subject(s) - chemistry , antioxidant , oxidative stress , eosinophil , receptor , pharmacology , glucocorticoid , cytokine , glucocorticoid receptor , peroxisome proliferator activated receptor , respiratory epithelium , endocrinology , medicine , immunology , asthma , biochemistry , respiratory system
Nitrated fatty acids (NFAs) are endogenous agonists of peroxisome proliferator‐activated receptor γ (PPAR‐γ) that have been shown to exhibit anti‐inflammatory and antioxidant activity. We investigated NFA effects in the OVA model of allergic airway disease. The glucocorticoid fluticasone (Flut) was used as a positive control. Pulmonary administration of the NFA 10‐nitro‐oleic acid (OA‐NO2) or Flut produced significant and essentially indistinguishable reductions in airway hyperresponsiveness, lung and BAL fluid cytokine concentrations, OVA‐specific IgE concentrations, and mucus production. Both likewise produced similar and significant reductions in eosinophil infiltration and oxidative stress, reflecting reduced adhesion molecule expression. In vitro studies using both immortalized and human bronchial epithelial cells cultured at an air‐liquid interface demonstrated that OA‐NO2 increased expression and activity of PPAR‐γ and decreased activity of the pro‐inflammatory transcription factor NF‐κB. Increased expression of the glucocorticoid receptor and activity of the antioxidant transcription factor Nrf2 were also observed. Our results thus demonstrate beneficial NFA effects that suggest potential therapeutic utility in asthma. This work was supported by National Institutes of Health grant HL093196.