D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma. J Lipid Res 2011 Mar;52(3):499-508
Date
12/07/2010Pubmed ID
21131532Pubmed Central ID
PMC3035686DOI
10.1194/jlr.M012724Scopus ID
2-s2.0-79953206963 (requires institutional sign-in at Scopus site) 60 CitationsAbstract
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.
Author List
Nandedkar SD, Weihrauch D, Xu H, Shi Y, Feroah T, Hutchins W, Rickaby DA, Duzgunes N, Hillery CA, Konduri KS, Pritchard KA JrAuthors
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of WisconsinDorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Apolipoprotein A-I
Asthma
Biomimetic Materials
Cell Count
Cholesterol, HDL
Collagen
Disease Models, Animal
Eosinophil Peroxidase
Eosinophils
Hypersensitivity
Immunoglobulin E
Lung
Male
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Oxidative Stress
Peptides
Pneumonia
Respiratory System
