title: Honey bee (Apis mellifera) venom induces AIM2 inflammasome activation in human keratinocytes.
abstract: BACKGROUND
  Following allergen exposure, cytokines and other pro-inflammatory signals play an important role in the immunological cascade leading to allergic sensitization. Inflammasomes sense exogenous and endogenous danger signals and trigger IL-1β and IL-18 activation which in turn shape Th2 responses. Honey bee venom (BV) allergies are very common; however, the local inflammatory cascade leading to the initiation of allergic sensitization is poorly understood. In this study, the local inflammatory cascades in skin after exposure to BV were investigated.
  
  
  METHODS
  The mechanisms of inflammasome activation in human skin and in cultured keratinocytes upon BV exposure were analyzed by ELISA, Western blot, flow cytometry, siRNA techniques, and immunofluorescence.
  
  
  RESULTS
  In an ex vivo bee sting model, BV induced IL-1β release suggesting the activation of inflammasomes. Indeed, in cultured keratinocytes, the BV component melittin triggered IL-1β and IL-18 release via the AIM2 inflammasome. AIM2 is a cytosolic DNA receptor, and mitochondrial as well as genomic DNA was detected in the cytosol of melittin-treated keratinocytes as triggers of inflammasome activation. As a mechanism, melittin mediated destruction of mitochondrial membranes leading to the leakage of mitochondrial DNA into the cytosolic compartment.
  
  
  CONCLUSIONS
  These data suggest that upon BV exposure, keratinocytes are involved in an innate immune response by the activation of the AIM2 inflammasome and subsequent IL-1β and IL-18 release triggered by endogenous DNA. As IL-1β and IL-18 are involved in Th2- and IgE-mediated immune reactions, these results could add to the understanding of the role of the tissue microenvironment to subsequent allergic responses.
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian-University, Munich, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Dombrowski
authors.forename: M
authors.initials: M
authors.lastname: Peric
authors.forename: S
authors.initials: S
authors.lastname: Koglin
authors.forename: N
authors.initials: N
authors.lastname: Kaymakanov
authors.forename: V
authors.initials: V
authors.lastname: Schmezer
authors.forename: M
authors.initials: M
authors.lastname: Reinholz
authors.forename: T
authors.initials: T
authors.lastname: Ruzicka
authors.forename: J
authors.initials: J
authors.lastname: Schauber
mesh_terms: D000818:Animals; D001514:Bee Venoms / Q000276:immunology*; D001516:Bees; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000502:physiology; D004268:DNA-Binding Proteins; D006801:Humans; D058847:Inflammasomes / Q000502:physiology*; D020382:Interleukin-18 / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism; D008555:Melitten / Q000494:pharmacology; D051336:Mitochondrial Membranes / Q000187:drug effects; D009687:Nuclear Proteins / Q000502:physiology*
chemical_list: C410167:AIM2 protein, human; D001514:Bee Venoms; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D009687:Nuclear Proteins; D008555:Melitten