title: Isotretinoin increases skin-surface levels of neutrophil gelatinase-associated lipocalin in patients treated for severe acne.
abstract: BACKGROUND
  A clear-cut need exists for safe and effective alternatives to the use of isotretinoin in severe acne. Lack of data regarding the specifics of isotretinoin's mechanism of action has hampered progress in this area. Recently, the protein neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a mediator of the apoptotic effect of isotretinoin on sebocytes.
  
  
  OBJECTIVE
  To establish further the clinical relevance of NGAL and to elucidate the factors that induce NGAL expression in sebocytes.
  
  
  METHODS
  Methods were developed to isolate and quantify skin-surface levels of NGAL from normal subjects and patients with acne undergoing treatment with isotretinoin.
  
  
  RESULTS
  Patients with acne were found to have higher skin levels of NGAL compared with normal subjects. Studies in SEB-1 sebocytes indicate that NGAL expression is increased in response to Propionibacterium acnes and interleukin (IL)-1β. In patients, isotretinoin increases NGAL levels by 2·4-fold on the skin surface and this increase precedes decreases in sebum and P. acnes counts.
  
  
  CONCLUSIONS
  These data support the hypothesis that NGAL is an important mediator of the early effects of isotretinoin on the sebaceous glands and provide insights into the mechanisms that regulate NGAL expression in the skin.
authors.affiliation: The Jake Gittlen Cancer Research Foundation, Department of Dermatology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Lumsden
authors.forename: A M
authors.initials: AM
authors.lastname: Nelson
authors.forename: M C
authors.initials: MC
authors.lastname: Dispenza
authors.forename: K L
authors.initials: KL
authors.lastname: Gilliland
authors.forename: Z
authors.initials: Z
authors.lastname: Cong
authors.forename: A L
authors.initials: AL
authors.lastname: Zaenglein
authors.forename: D M
authors.initials: DM
authors.lastname: Thiboutot
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy* / Q000378:metabolism; D000209:Acute-Phase Proteins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D015331:Cohort Studies; D003879:Dermatologic Agents / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D015474:Isotretinoin / Q000627:therapeutic use*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D011425:Propionibacterium acnes / Q000302:isolation & purification / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012627:Sebaceous Glands / Q000166:cytology / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D003879:Dermatologic Agents; D053583:Interleukin-1beta; D016209:Interleukin-8; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D015474:Isotretinoin