19 research outputs found
Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds
© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds
The key role of corneocytes in pityrosporoses.
Pityrosporoses encompass various Malassezia-driven conditions. Dandruff and seborrheic dermatitis are members of this family of disorders. Their precise pathomechanisms have not been completely elucidated so far. This review focuses on the role of corneocytes in these disorders. Malassezia yeasts are not evenly distributed at the surface of the stratum corneum. Rather, they are clumped on some corneocytes while other corneocytes in their vicinity are almost free of these microorganisms. The corneocytes heavily coated by yeasts suggest a cell-related defect in the mechanisms controlling the skin biocene including the natural antimicrobial peptides and nitric oxide. Most environmental factors influencing pityrosporoses indeed affect the natural human defenses against certain microorganisms. We frame as a hypothesis that the primary defect in some Malassezia-driven disorders resides in the corneocytes and their precursor keratinocytes