title: Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne?
abstract: BACKGROUND
  The main function of the human sebaceous gland is sebum excretion. Increased sebum levels combined with follicular hyperkeratinization are a prerequisite of acne vulgaris. As peroxisome proliferator-activated receptors (PPARs) are known to control lipid metabolism in several human tissues they have been considered to be involved in the pathogenesis of acne vulgaris.
  
  
  OBJECTIVE
  To investigate the effect of activators of PPAR-α (WY14643), PPAR-γ (rosiglitazone) and PPAR-δ (L-165.041) on basal and staurosporine-induced apoptosis in the human sebocyte cell line SZ95 in vitro.
  
  
  METHODS
  After defining the basal effects of PPAR activators on membrane integrity (lactate dehydrogenase release) and DNA synthesis (5-bromodeoxyuridine incorporation), apoptosis was determined by the release of histone-associated DNA fragments. The underlying signalling events were detected by Western blotting and the use of specific inhibitors against p44/42 and protein kinase B (PKB)/Akt.
  
  
  RESULTS
  PPAR activators of all three subsets offer antiapoptotic effects, with L-165.041 being the most potent. This compound induced the activation of PKB/Akt and p44/42, two kinases involved in antiapoptosis and proliferation, respectively. An inhibition of these kinases by specific inhibitors reversed the suppression of histone-associated DNA fragments by L-165.041, indicating that these signalling pathways participate in the observed antiapoptotic effect.
  
  
  CONCLUSIONS
  The present data suggest that activators of PPAR, in particular of the δ subset, might have beneficial effects on acne vulgaris by inhibiting the release of lipids in the context of sebocyte apoptosis.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Hospital, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, Frankfurt/Main 60590, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schuster
authors.forename: C C
authors.initials: CC
authors.lastname: Zouboulis
authors.forename: F
authors.initials: F
authors.lastname: Ochsendorf
authors.forename: J
authors.initials: J
authors.lastname: Müller
authors.forename: D
authors.initials: D
authors.lastname: Thaçi
authors.forename: A
authors.initials: A
authors.lastname: Bernd
authors.forename: R
authors.initials: R
authors.lastname: Kaufmann
authors.forename: S
authors.initials: S
authors.lastname: Kippenberger
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D047493:PPAR alpha / Q000494:pharmacology; D047494:PPAR delta / Q000494:pharmacology; D047495:PPAR gamma / Q000494:pharmacology; D047492:Peroxisome Proliferator-Activated Receptors / Q000494:pharmacology*; D010642:Phenoxyacetates / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D000077154:Rosiglitazone; D012627:Sebaceous Glands / Q000166:cytology* / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D004791:Enzyme Inhibitors; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D010642:Phenoxyacetates; D011743:Pyrimidines; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C006253:pirinixic acid; D007770:L-Lactate Dehydrogenase; D001973:Bromodeoxyuridine; D019311:Staurosporine