D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma.
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.
Department of Pediatric Surgery, Medical College of Wisconsin, Children's Research Institute, Zablocki Veterans Administration Medical Center, Milwaukee, WI, USA.
S D
SD
Nandedkar
D
D
Weihrauch
H
H
Xu
Y
Y
Shi
T
T
Feroah
W
W
Hutchins
D A
DA
Rickaby
N
N
Duzgunes
C A
CA
Hillery
K S
KS
Konduri
K A
KA
Pritchard
D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002452:Cell Count; D008076:Cholesterol, HDL / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D006967:Hypersensitivity / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011014:Pneumonia / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D010455:Peptides; D007073:Immunoglobulin E; D003094:Collagen; D047209:Eosinophil Peroxidase