More finger pointing towards the peptide LL-37 and its role in the inflammation associated with rosacea.

This abstract tells us that the inflammation and extra blood vessels associated with exposure to the sun (specifically the UVB band of radiation) are enhanced in the presence of cathelicidin LL-37.

This result may help explain why sun exposure is one of the most commonly quoted rosacea triggers.

Cathelicidin has been in the rosacea news since around 2002, gaining publicity because of the discoveries like the fact that rosacea sufferers have abnormally high levels of cathelicidin in their facial skin.

Abstract

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

Journal of Dermatological Science

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

Department of Dermatology and Allergy, Ludwig-Maximilian-University, Munich, Germany

HIGHLIGHTS

• UVB triggers inflammasome mediated IL-1β release by keratinocytes.
• LL-37 enhances UV-induced IL-1β secretion by acting on the P2X₇ receptor.
• P2X₇ receptor activation results in an increase in intracellular calcium concentrations.
• IL-1β and LL-37 work synergistically to promote angiogenesis.
• LL-37 augments the proinflammatory and proangiogenic effects of UVB.

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.

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• Read the NRS articles on cathelicidins
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• Gallo to trial Aminocaproic Acid as Cathelicidin Inhibitor
• NRS Blog: cathelicidins show allergic basis for rosacea ?
• Glyco Mira developing anti-cathelicidin treatment ?
• Doxycycline can deactivate Cathelicidins