Abstract
Asthma is characterized by oxidative stress and inflammation of the airways. Although proinflammatory lipids are involved in asthma, therapies targeting them remain lacking. Ac-DWFKAFYDKVAEKFKEAFNH(2) (4F) is an apolipoprotein (apo)A-I mimetic that has been shown to preferentially bind oxidized lipids and improve HDL function. The objective of the present study was to determine the effects of 4F on oxidative stress, inflammation, and airway resistance in an established murine model of asthma. We show here that ovalbumin (OVA)-sensitization increased airway hyperresponsiveness, eosinophil recruitment, and collagen deposition in lungs of C57BL/6J mice by a mechanism that could be reduced by 4F. OVA sensitization induced marked increases in transforming growth factor (TGF)β-1, fibroblast specific protein (FSP)-1, anti-T15 autoantibody staining, and modest increases in 4-hydroxynonenal (4-HNE) Michael's adducts in lungs of OVA-sensitized mice. 4F decreased TGFβ-1, FSP-1, anti-T15 autoantibody, and 4-HNE adducts in the lungs of the OVA-sensitized mice. Eosinophil peroxidase (EPO) activity in bronchial alveolar lavage fluid (BALF), peripheral eosinophil counts, total IgE, and proinflammatory HDL (p-HDL) were all increased in OVA-sensitized mice. 4F decreased BALF EPO activity, eosinophil counts, total IgE, and p-HDL in these mice. These data indicate that 4F reduces pulmonary inflammation and airway resistance in an experimental murine model of asthma by decreasing oxidative stress.
Highlights
Asthma is characterized by oxidative stress and inflammation of the airways
Asthma accounts for the most hospitalizations and missed school and parent workdays with an estimated cost of $12 billion per year [2]. It is characterized by chronic inflammation, airway hyperresponsiveness (AHR), collagen deposition, and airway remodeling, which may lead to progressive irreversible lung damage
At the time of euthanasia, samples were collected from a separate set of mice for eosinophil peroxidase (EPO) in bronchial alveolar lavage fluid (BALF), lung histology, peripheral blood eosinophils, total IgE, and proinflammatory HDL (p-HDL) levels as we described before [19, 21]
Summary
Asthma is characterized by oxidative stress and inflammation of the airways. proinflammatory lipids are involved in asthma, therapies targeting them remain lacking. We show here that ovalbumin (OVA)-sensitization increased airway hyperresponsiveness, eosinophil recruitment, and collagen deposition in lungs of C57BL/6J mice by a mechanism that could be reduced by 4F. 4F decreased BALF EPO activity, eosinophil counts, total IgE, and p-HDL in these mice These data indicate that 4F reduces pulmonary inflammation and airway resistance in an experimental murine model of asthma by decreasing oxidative stress.—Nandedkar, S. Asthma accounts for the most hospitalizations and missed school and parent workdays with an estimated cost of $12 billion per year [2] It is characterized by chronic inflammation, airway hyperresponsiveness (AHR), collagen deposition, and airway remodeling, which may lead to progressive irreversible lung damage.
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