TY - JOUR
T1 - Cathelicidin peptide LL-37 increases UVB-triggered inflammasome activation
T2 - Possible implications for rosacea
AU - Salzer, Suzanna
AU - Kresse, Sonja
AU - Hirai, Yoji
AU - Koglin, Sarah
AU - Reinholz, Markus
AU - Ruzicka, Thomas
AU - Schauber, Jürgen
N1 - Funding Information:
This work was supported by the Deutsche Forschungsgemeinschaft ( Scha 979/5-1 ) and Else Kroener Fresenius Stiftung ( 2012_A119 ).
Publisher Copyright:
© 2014 Japanese Society for Investigative Dermatology.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Cathelicidin LL-37
KW - Inflammasome
KW - P2X
KW - Rosacea
KW - UVB
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U2 - 10.1016/j.jdermsci.2014.09.002
DO - 10.1016/j.jdermsci.2014.09.002
M3 - Article
C2 - 25306296
AN - SCOPUS:84919492128
VL - 76
SP - 173
EP - 179
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
SN - 0923-1811
IS - 3
ER -