title: Peroxisome proliferator-activated receptor alpha regulates skin inflammation and humoral response in atopic dermatitis.
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.
  
  
  CONCLUSIONS
  PPAR-alpha acts as a negative regulator of skin inflammation in AD.
authors.affiliation: Inserm U547, Lille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Staumont-Sallé
authors.forename: Georges
authors.initials: G
authors.lastname: Abboud
authors.forename: Céline
authors.initials: C
authors.lastname: Brénuchon
authors.forename: Akira
authors.initials: A
authors.lastname: Kanda
authors.forename: Thomas
authors.initials: T
authors.lastname: Roumier
authors.forename: Céline
authors.initials: C
authors.lastname: Lavogiez
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fleury
authors.forename: Patrick
authors.initials: P
authors.lastname: Rémy
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Papin
authors.forename: Justine
authors.initials: J
authors.lastname: Bertrand-Michel
authors.forename: François
authors.initials: F
authors.lastname: Tercé
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Delaporte
authors.forename: Monique
authors.initials: M
authors.lastname: Capron
authors.forename: David
authors.initials: D
authors.lastname: Dombrowicz
mesh_terms: D000279:Administration, Cutaneous; D000287:Administration, Topical; D000328:Adult; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D007074:Immunoglobulin G; D018836:Inflammation Mediators; D047493:PPAR alpha; D011743:Pyrimidines; D007073:Immunoglobulin E; C006253:pirinixic acid; D010047:Ovalbumin