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.
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.
Authors: Allan C Just; Robin M Whyatt; Matthew S Perzanowski; Antonia M Calafat; Frederica P Perera; Inge F Goldstein; Qixuan Chen; Andrew G Rundle; Rachel L Miller Journal: Environ Health Perspect Date: 2012-06-26 Impact factor: 9.031
Authors: Devi Rani Sagar; A Gemma Gaw; Bright N Okine; Stephen G Woodhams; Amy Wong; David A Kendall; Victoria Chapman Journal: Mol Pain Date: 2009-10-08 Impact factor: 3.395