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J Allergy Clin Immunol. 2008 Apr;121(4):962-8.e6. doi: 10.1016/j.jaci.2007.12.1165. Epub 2008 Feb 4.

Peroxisome proliferator-activated receptor alpha regulates skin inflammation and humoral response in atopic dermatitis.

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Inserm U547, Lille, France.



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.


We have investigated the role of PPAR-alpha in the regulation of atopic dermatitis (AD), a common skin inflammatory disease.


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.


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.


PPAR-alpha acts as a negative regulator of skin inflammation in AD.

[Indexed for MEDLINE]

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