D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma[S]
Asthma is characterized by oxidative stress and inflammation of the airways. Although proinflammatory lipids are involved in asthma, therapies targeting them remain lacking. Ac-DW F KA F YDKVAEK F KEA F NH2 (4F) is an apolipoprotein (apo)A-I mimetic that has been shown to preferentially bind oxidize...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2011-03-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520409307 |
| _version_ | 1818899270024036352 |
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| author | S.D. Nandedkar D. Weihrauch H. Xu Y. Shi T. Feroah W. Hutchins D.A. Rickaby N. Duzgunes C.A. Hillery K.S. Konduri Jr.K.A. Pritchard |
| author_facet | S.D. Nandedkar D. Weihrauch H. Xu Y. Shi T. Feroah W. Hutchins D.A. Rickaby N. Duzgunes C.A. Hillery K.S. Konduri Jr.K.A. Pritchard |
| author_sort | S.D. Nandedkar |
| collection | DOAJ |
| description | Asthma is characterized by oxidative stress and inflammation of the airways. Although proinflammatory lipids are involved in asthma, therapies targeting them remain lacking. Ac-DW F KA F YDKVAEK F KEA F NH2 (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. |
| first_indexed | 2024-12-19T19:45:17Z |
| format | Article |
| id | doaj.art-4d97eaf56a414e7594ef8fdbe2978d00 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T19:45:17Z |
| publishDate | 2011-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-4d97eaf56a414e7594ef8fdbe2978d002022-12-21T20:08:09ZengElsevierJournal of Lipid Research0022-22752011-03-01523499508D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma[S]S.D. Nandedkar0D. Weihrauch1H. Xu2Y. Shi3T. Feroah4W. Hutchins5D.A. Rickaby6N. Duzgunes7C.A. Hillery8K.S. Konduri9Jr.K.A. Pritchard10Departments of Pediatric Surgery, Zablocki Veterans Administration Medical Center, Milwaukee, WIDepartments of Anesthesiology, Zablocki Veterans Administration Medical Center, Milwaukee, WIDepartments of Pediatric Surgery, Zablocki Veterans Administration Medical Center, Milwaukee, WIDepartments of Pediatric Surgery, Zablocki Veterans Administration Medical Center, Milwaukee, WIDepartments of Pediatrics, Zablocki Veterans Administration Medical Center, Milwaukee, WIDepartments of Pediatrics, Zablocki Veterans Administration Medical Center, Milwaukee, WIDepartments of Medicine, Medical College of Wisconsin, Children's Research Institute, Zablocki Veterans Administration Medical Center, Milwaukee, WIDepartment of Microbiology, University of the Pacific School of Dentistry, San Francisco, CADepartments of Pediatrics, Zablocki Veterans Administration Medical Center, Milwaukee, WIDepartments of Pediatrics, Zablocki Veterans Administration Medical Center, Milwaukee, WITo whom correspondence should be addressed. kpritch@mcw.edu; Departments of Pediatric Surgery, Zablocki Veterans Administration Medical Center, Milwaukee, WIAsthma is characterized by oxidative stress and inflammation of the airways. Although proinflammatory lipids are involved in asthma, therapies targeting them remain lacking. Ac-DW F KA F YDKVAEK F KEA F NH2 (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.http://www.sciencedirect.com/science/article/pii/S0022227520409307apolipoproteinairway resistanceproinflammatory lipids |
| spellingShingle | S.D. Nandedkar D. Weihrauch H. Xu Y. Shi T. Feroah W. Hutchins D.A. Rickaby N. Duzgunes C.A. Hillery K.S. Konduri Jr.K.A. Pritchard D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma[S] Journal of Lipid Research apolipoprotein airway resistance proinflammatory lipids |
| title | D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma[S] |
| title_full | D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma[S] |
| title_fullStr | D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma[S] |
| title_full_unstemmed | D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma[S] |
| title_short | D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma[S] |
| title_sort | d 4f an apoa 1 mimetic decreases airway hyperresponsiveness inflammation and oxidative stress in a murine model of asthma s |
| topic | apolipoprotein airway resistance proinflammatory lipids |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520409307 |
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