title: Cathelicidin peptide LL-37 increases UVB-triggered inflammasome activation: possible implications for rosacea.
abstract: BACKGROUND
  In patients with rosacea, environmental stressors, especially UVB radiation, trigger disease flares that are characterized by inflammation and vascular hyperactivity. An altered innate immune detection and response system, modulated to a large extent by the aberrant production and processing of human cathelicidin LL-37, is thought to play a central role in disease pathogenesis.
  
  
  OBJECTIVE
  To investigate whether the proinflammatory and proangiogenic effects of UV radiation are enhanced in the presence of cathelicidin LL-37.
  
  
  METHODS
  Human skin ex vivo and epidermal keratinocytes in vitro were exposed to UVB irradiation. The proinflammatory effects of UVB exposure in the presence and absence of LL-37 were characterized using immunoblot, transfection, qPCR, and a cell-based second messenger assay. ELISA was used to assess cytokine release and the angiogenic potential of endothelial cells was evaluated using an in vitro angiogenesis assay.
  
  
  RESULTS
  UVB irradiation triggered the inflammasome-mediated processing and release of IL-1β. LL-37 augmented this UV-induced IL-1β secretion by acting on the P2X7 receptor on keratinocytes. P2X7 receptor activation by UVB and LL-37 resulted in an increase in intracellular calcium concentrations, which enhances inflammasome activation and subsequent IL-1β release. Furthermore, IL-1β and LL-37 worked synergistically to increase the angiogenic potential of endothelial cells.
  
  
  CONCLUSIONS
  Cathelicidin LL-37 modulates the proinflammatory and proangiogenic effects of UV radiation and thereby contributes to enhanced sensitivity to sun exposure in rosacea.
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian-University, Frauenlobstr. 9-11, Munich 80337, Germany.
authors.forename: Suzanna
authors.initials: S
authors.lastname: Salzer
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian-University, Frauenlobstr. 9-11, Munich 80337, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kresse
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian-University, Frauenlobstr. 9-11, Munich 80337, Germany.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hirai
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian-University, Frauenlobstr. 9-11, Munich 80337, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Koglin
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian-University, Frauenlobstr. 9-11, Munich 80337, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Reinholz
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian-University, Frauenlobstr. 9-11, Munich 80337, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian-University, Frauenlobstr. 9-11, Munich 80337, Germany. Electronic address: juergen.schauber@med.uni-muenchen.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schauber
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism* / Q000528:radiation effects*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D009389:Neovascularization, Pathologic / Q000209:etiology; D011836:Radiation Tolerance / Q000502:physiology; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D012393:Rosacea / Q000209:etiology* / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D058847:Inflammasomes; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D058486:Receptors, Purinergic P2X7; D002118:Calcium; D054804:Cathelicidins
keywords: Angiogenesis; Cathelicidin LL-37; Inflammasome; P2X(7); Rosacea; UVB