Peroxisome proliferator-activated receptor alpha regulates skin inflammation and humoral response in atopic dermatitis
| Autor: | Justine Bertrand-Michel, Céline Brénuchon, François Tercé, Monique Capron, Akira Kanda, Sébastien Fleury, Thomas Roumier, Patrick Rémy, Céline Lavogiez, Bart Staels, David Dombrowicz, J P Papin, Delphine Staumont-Sallé, Emmanuel Delaporte, Georges Abboud |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Thymic stromal lymphopoietin Ovalbumin Administration Topical Immunology Peroxisome proliferator-activated receptor Inflammation Biology Administration Cutaneous Dermatitis Atopic Mice Immune system medicine Immunology and Allergy Animals Humans PPAR alpha Receptor chemistry.chemical_classification Mice Knockout Mice Inbred BALB C integumentary system Atopic dermatitis Immunoglobulin E medicine.disease Disease Models Animal medicine.anatomical_structure Pyrimidines chemistry Immunoglobulin G Female Peroxisome proliferator-activated receptor alpha medicine.symptom Bronchial Hyperreactivity Inflammation Mediators Keratinocyte |
| Zdroj: | The Journal of allergy and clinical immunology. 121(4) |
| ISSN: | 1097-6825 |
| Popis: | Background The peroxisome proliferator-activated receptors (PPARs) α, 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-α 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-α 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-α–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 T H 2 and, to a greater extent, T H 1 responses and to increased skin expression of nuclear factor κB. Interestingly, PPAR-α expression was decreased in eczematous skin from patients with AD compared with skin from nonatopic donors, suggesting that defective PPAR-α expression might contribute to the pathology. Topical application of WY14643, a specific PPAR-α agonist, significantly decreased antigen-induced skin inflammation in the AD model. Conclusion PPAR-α acts as a negative regulator of skin inflammation in AD. |
| Databáze: | OpenAIRE |
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