Cathelicidin peptide LL-37 increases UVB-triggered inflammasome activation: Possible implications for rosacea

Suzanna Salzer, Sonja Kresse, Yoji Hirai, Sarah Koglin, Markus Reinholz, Thomas Ruzicka, Jürgen Schauber

Research output: Contribution to journalArticle

29 Citations (Scopus)

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. Conclusion: Cathelicidin LL-37 modulates the proinflammatory and proangiogenic effects of UV radiation and thereby contributes to enhanced sensitivity to sun exposure in rosacea.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalJournal of dermatological science
Volume76
Issue number3
DOIs
Publication statusPublished - Dec 1 2014
Externally publishedYes

Keywords

  • Angiogenesis
  • Cathelicidin LL-37
  • Inflammasome
  • P2X
  • Rosacea
  • UVB

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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