rss Posted October 13, 2014 Report Share Posted October 13, 2014 Cathelicidin peptide LL-37 increases UVB-triggered inflammasome activation: Possible implications for rosacea. J Dermatol Sci. 2014 Sep 28; Authors: Salzer S, Kresse S, Hirai Y, Koglin S, Reinholz M, Ruzicka T, Schauber J 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-1Î². LL-37 augmented this UV-induced IL-1Î² 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-1Î² release. Furthermore, IL-1Î² 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.PMID: 25306296 [PubMed - as supplied by publisher] http://www.ncbi.nlm.nih.gov/pubmed/25306296?dopt=Abstract = URL to article Link to comment Share on other sites More sharing options...
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