Peroxisome proliferator-activated receptor ⍺ regulates skin inflammation and humoral response in atopic dermatitis - 15/08/11
, Georges Abboud, BSc a, b, c, , Céline Brénuchon, MD a, b, c, Akira Kanda, MD, PhD a, b, c, Thomas Roumier, PhD a, b, c, Céline Lavogiez, MD a, b, c, d, Sébastien Fleury a, b, c, Patrick Rémy a, b, c, Jean-Paul Papin a, b, c, Justine Bertrand-Michel e, f, François Tercé, PhD e, f, g, Bart Staels, PhD b, c, h, Emmanuel Delaporte, MD c, d, Monique Capron, PhD a, b, c, David Dombrowicz, PhD a, b, c, ⁎ 
Reprint requests: David Dombrowicz, PhD, Inserm U547, Institut Pasteur de Lille 1, rue Prof Calmette BP245, 59019 Lille Cedex, France.Abstract |
Background |
The peroxisome proliferator-activated receptors (PPARs) ⍺, β/δ, and γ are ligand-activated transcription factors belonging to the nuclear receptor superfamily. In addition to their regulatory role on lipid and glucose metabolism, they exert anti-inflammatory properties. In skin both PPAR-⍺ and PPAR-β/δ regulate keratinocyte proliferation/differentiation and contribute to wound healing. The 3 PPAR isoforms are expressed by several cell types recruited into the dermis during inflammation.
Objective |
We have investigated the role of PPAR-⍺ in the regulation of atopic dermatitis (AD), a common skin inflammatory disease.
Methods |
We chose a mouse model of inflammatory dermatosis with immunologic features of AD and used epicutaneous sensitization with ovalbumin in the absence of adjuvant, which mimics the human pathology.
Results |
On antigen sensitization, PPAR-⍺–deficient mice display increased epidermal thickening, dermal recruitment of inflammatory cells, lung inflammation, airway hyperresponsiveness, and IgE and IgG2a production compared with their wild-type counterparts. Increased inflammation was correlated to an enhancement of TH2 and, to a greater extent, TH1 responses and to increased skin expression of nuclear factor κB. Interestingly, PPAR-⍺ expression was decreased in eczematous skin from patients with AD compared with skin from nonatopic donors, suggesting that defective PPAR-⍺ expression might contribute to the pathology. Topical application of WY14643, a specific PPAR-⍺ agonist, significantly decreased antigen-induced skin inflammation in the AD model.
Conclusion |
PPAR-⍺ acts as a negative regulator of skin inflammation in AD.
Le texte complet de cet article est disponible en PDF.Key words : Peroxisome proliferator-activated receptor ⍺, atopic dermatitis, allergy, inflammation, human, mouse
Abbreviations used : AD, AHR, BAL, NF-κB, OVA, Penh, PPAR, TEWL, TSLP, WT
Plan
| Supported by grants from Inserm, Université Lille 2 and Institut Pasteur de Lille and by a fellowship (to D.S.) from Inserm. |
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| Disclosure of potential conflict of interest: D. Dombrowicz has received research support from Inserm, Université Lille 2, Institut Pasteur de Lille, ANR, FRM, the European Union, and Region Nord-Pas de Calais. M. Capron has received research support from Inserm, Université Lille 2, and Institut Pasteur de Lille. The rest of the authors have declared that they have no conflict of interest. |
Vol 121 - N° 4
P. 962 - avril 2008 Retour au numéro
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