Allergic asthma is characterized by airway hyperresponsiveness, eosinophilia, and mucus accumulation and is associated with increased IgE concentrations. We demonstrate here that peroxisome proliferator–activated receptors (PPARs), PPAR-α and PPAR-γ, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced airway hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma. In addition, we demonstrate that PPAR-α and -γ are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity. Thus, PPAR-α and -γ (co)agonists might be of therapeutic interest for the regulation of allergic or inflammatory reactions by targeting both regulatory and effector cells involved in the immune response.
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4 August 2003
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August 04 2003
Peroxisome Proliferator–activated Receptors α and γ Down-regulate Allergic Inflammation and Eosinophil Activation
Gaetane Woerly,
Gaetane Woerly
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
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Kohei Honda,
Kohei Honda
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
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Marc Loyens,
Marc Loyens
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
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Jean-Paul Papin,
Jean-Paul Papin
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
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Johan Auwerx,
Johan Auwerx
3Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS)/INSERM/Université Louis Pasteur, 67401 Ilkirch, France
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Bart Staels,
Bart Staels
2INSERM U545, Institut Pasteur de Lille and Faculté de Pharmacie, Université de Lille II, 59019 Lille, France
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Monique Capron,
Monique Capron
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
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David Dombrowicz
David Dombrowicz
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
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Gaetane Woerly
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
Kohei Honda
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
Marc Loyens
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
Jean-Paul Papin
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
Johan Auwerx
3Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS)/INSERM/Université Louis Pasteur, 67401 Ilkirch, France
Bart Staels
2INSERM U545, Institut Pasteur de Lille and Faculté de Pharmacie, Université de Lille II, 59019 Lille, France
Monique Capron
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
David Dombrowicz
1Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, 59019 Lille, France
Address correspondence to David Dombrowicz, Institut National de la Santé et de la Recherche Médicale U547, Institut Pasteur de Lille 1, rue Prof. Calmette BP245, 59019 Lille Cedex, France. Phone: 33-03-20-87-79-67; Fax: 33-03-20-87-78-88; email: [email protected]
*
Abbreviations used in this paper: ADCC, antibody-dependent cellular cytoxicity; AHR, airway hyperresponsiveness; BAL, bronchoalveolar lavage; LTB4, leukotriene B4; PAS, periodic acid schiff; PPAR, peroxisome proliferator–activated receptor; RT, reverse transcriptase; WT, wild-type.
Received:
August 09 2002
Revision Received:
June 12 2003
Accepted:
June 12 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 198 (3): 411–421.
Article history
Received:
August 09 2002
Revision Received:
June 12 2003
Accepted:
June 12 2003
Citation
Gaetane Woerly, Kohei Honda, Marc Loyens, Jean-Paul Papin, Johan Auwerx, Bart Staels, Monique Capron, David Dombrowicz; Peroxisome Proliferator–activated Receptors α and γ Down-regulate Allergic Inflammation and Eosinophil Activation . J Exp Med 4 August 2003; 198 (3): 411–421. doi: https://doi.org/10.1084/jem.20021384
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