Rosacea: The Blessing of the Celts - An Approach to Pathogenesis Through Translational Research.

Rosacea: The Blessing of the Celts - An Approach to Pathogenesis Through Translational Research. Acta Derm Venereol. 2015 Aug 25; Authors: Melnik BC Abstract Increased expression of cathelicidin antimicrobial peptide (CAMP) is related to the pathogenesis of rosacea. CAMP plays a crucial role in antimicrobial defences, such as the killing of mycobacteria. CAMP gene expression is regulated by vitamin D-dependent (VDR) and vitamin D-independent (C/EBPα) transcription factors. VDR-dependent CAMP expression is sufficient during the summer months in Nordic countries, but insufficient during Nordic winters, due to low ultraviolet (UV) levels. Historically, the Celts may have overcome this geographical disadvantage of deficient CAMP production during the winter through an as-yet undefined acquired mutation that activates the alternative vitamin D-independent CAMP promoter C/EBPα. C/EBPα is the downstream transcription factor of Toll-like receptor (TLR)-mediated innate immune reactions and endoplasmic reticulum (ER) stress responses. At the molecular level, all clinical trigger factors for rosacea can be regarded as ER stressors. A mutation-based upregulation of ER stress responsiveness in rosacea may thus explain patients' reduced threshold for ER stressors. It is notable that ER stress upregulates the potent lipid-mediator sphingosine-1-phosphate (S1P), which explains multiple pathological aberrations observed in rosacea skin. Enhanced E...
Source: Acta Dermato-Venereologica - Category: Dermatology Authors: Tags: Acta Derm Venereol Source Type: research