title: Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne.
abstract: BACKGROUND
  Acne is a common disorder of the human pilosebaceous unit, yet the mechanisms underlying hyperkeratinisation and subsequent inflammation (comedogenesis) remain to be determined, although cutaneous pathogens are implicated. Previously, it was reported that the release of the cytokine interleukin-1α (IL-1α) by keratinocytes of the sebaceous duct was pivotal in the life cycle of the comedone, mediating both its development and its spontaneous resolution. Toll-like receptors are a family of molecules that recognise pathogen associated molecular patterns (PAMPs) presented by microorganisms, initiating a signalling cascade terminating in the release of antimicrobial compounds and cytokines.
  
  
  METHODS
  We used ex vivo sebaceous gland and primary monolayer keratinocyte culture, alongside ELISAs, immunohistochemistry, Western blotting and RT-PCR to investigate the contribution of TLR activation to acne pathogenesis.
  
  
  RESULTS
  We found TLR2 to be expressed in basal and infundibular keratinocytes, and sebaceous glands, and its activation provoked the release of IL-1α from primary human keratinocytes in vitro. The exposure of microdissected human sebaceous glands to PAMPs specific for TLR2 in vitro resulted in a pattern of IL-1α like cornification after seven days of exposure.
  
  
  CONCLUSIONS
  TLR activation and secretion of IL-1α from keratinocytes may be initiating steps in comedogenesis and, therefore, critical to the pathophysiology of acne.
authors.affiliation: The Clore Laboratory, University of Buckingham, Hunter Street, Buckingham MK18 1EG, UK. joanne.selway@buckingham.ac.uk.
authors.forename: Joanne Louise
authors.initials: JL
authors.lastname: Selway
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kurczab
authors.forename: Terence
authors.initials: T
authors.lastname: Kealey
authors.forename: Kenneth
authors.initials: K
authors.lastname: Langlands
mesh_terms: D000152:Acne Vulgaris / Q000209:etiology / Q000378:metabolism*; D000368:Aged; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053582:Interleukin-1alpha / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012627:Sebaceous Glands / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism* / Q000502:physiology
chemical_list: D053582:Interleukin-1alpha; D051195:Toll-Like Receptor 2