Peroxisome proliferator-activated receptor alpha regulates skin inflammation and humoral response in atopic dermatitis.
J Allergy Clin Immunol
; 121(4): 962-8.e6, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18249437
ABSTRACT
BACKGROUND:
The peroxisome proliferator-activated receptors (PPARs) alpha, beta/delta, and gamma 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-alpha and PPAR-beta/delta 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-alpha 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-alpha-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 kappaB. Interestingly, PPAR-alpha expression was decreased in eczematous skin from patients with AD compared with skin from nonatopic donors, suggesting that defective PPAR-alpha expression might contribute to the pathology. Topical application of WY14643, a specific PPAR-alpha agonist, significantly decreased antigen-induced skin inflammation in the AD model.CONCLUSION:
PPAR-alpha acts as a negative regulator of skin inflammation in AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina E
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Imunoglobulina G
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Mediadores da Inflamação
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PPAR alfa
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Dermatite Atópica
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article