title: TRAIL contributes to the apoptotic effect of 13-cis retinoic acid in human sebaceous gland cells.
abstract: BACKGROUND
  The full mechanism of action of isotretinoin [13-cis retinoic acid (13-cis RA)] in treating acne is unknown. 13-cis RA induces key genes in sebocytes that are involved in apoptosis, including Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL).
  
  
  OBJECTIVE
  In this study, we investigated the role of 13-cis RA-induced TRAIL within SEB-1 sebocytes.
  
  
  METHODS
  Using 13-cis RA and recombinant human TRAIL (rhTRAIL) protein, we assessed induction of TRAIL and apoptosis in SEB-1 sebocytes, normal keratinocytes and patient skin biopsies.
  
  
  RESULTS
  Treatment with rhTRAIL protein increased TUNEL-positive staining in SEB-1 sebocytes. TRAIL siRNA significantly decreased the percentage of TUNEL-positive SEB-1 sebocytes in response to 13-cis RA treatment. Furthermore, TRAIL expression increased in the skin of patients with acne after 1 week of isotretinoin therapy compared with baseline. TRAIL expression localized within sebaceous glands. Unlike sebocytes, TRAIL protein expression was not increased in normal human epidermal keratinocytes in response to 13-cis RA, nor did rhTRAIL induce apoptosis in keratinocytes, suggesting that TRAIL is key in the sebocyte-specific apoptotic effects of 13-cis RA.
  
  
  CONCLUSIONS
  Taken together, our data suggest that TRAIL, like the neutrophil gelatinase-associated lipocalin, is involved in mediating 13-cis RA apoptosis of sebocytes.
authors.affiliation: The Jake Gittlen Cancer Research Foundation and Department of Dermatology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Nelson
authors.forename: Z
authors.initials: Z
authors.lastname: Cong
authors.forename: K L
authors.initials: KL
authors.lastname: Gilliland
authors.forename: D M
authors.initials: DM
authors.lastname: Thiboutot
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000209:Acute-Phase Proteins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D015474:Isotretinoin / Q000494:pharmacology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012627:Sebaceous Glands / Q000166:cytology* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection
chemical_list: D000209:Acute-Phase Proteins; D003879:Dermatologic Agents; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D015474:Isotretinoin