Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands. We have previously shown that a non-psychotropic phytocannabinoid ((-)-cannabidiol [CBD]) exerted complex anti-acne effects by normalizing 'pro-acne agents'-induced excessive sebaceous lipid production, reducing proliferation and alleviating inflammation in human SZ95 sebocytes. Therefore, in this study we aimed to explore the putative anti-acne effects of further non-psychotropic phytocannabinoids ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], (-)-cannabigerol [CBG], (-)-cannabigerovarin [CBGV] and (-)-Δ(9) -tetrahydrocannabivarin [THCV]). Viability and proliferation of human SZ95 sebocytes were investigated by MTT and CyQUANT assays; cell death and lipid synthesis were monitored by DilC1 (5)-SYTOX Green labelling and Nile Red staining, respectively. Inflammatory responses were investigated by monitoring expressions of selected cytokines upon lipopolysaccharide treatment (RT-qPCR, ELISA). Up to 10 μm, the phytocannabinoids only negligibly altered the viability of the sebocytes, whereas high doses (≥50 μm) induced apoptosis. Interestingly, basal sebaceous lipid synthesis was differentially modulated by the substances: CBC and THCV suppressed it, and CBDV had only minor effects, whereas CBG and CBGV increased it. Importantly, CBC, CBDV and THCV significantly reduced arachidonic acid (AA)-induced 'acne-like' lipogenesis. Moreover, THCV suppressed proliferation, and all phytocannabinoids exerted remarkable anti-inflammatory actions. Our data suggest that CBG and CBGV may have potential in the treatment of dry-skin syndrome, whereas CBC, CBDV and especially THCV show promise to become highly efficient, novel anti-acne agents. Moreover, based on their remarkable anti-inflammatory actions, phytocannabinoids could be efficient, yet safe novel tools in the management of cutaneous inflammations.

The investigated Ec. extract shows great potential in alleviating cutaneous symptoms of AE, and by exerting remarkable anti-inflammatory actions and restoring the epidermal lipid barrier, it will be very likely a well-tolerated, powerful novel ingredient for the adjuvant therapy of AE.

Polyols (e.g. glycerol, xylitol) are implicated as moisturizers of the skin and other epithelial tissues. However, we lack information about their exact cellular mechanisms and their effects on the gene expression profiles. Therefore, in this study, we aimed at investigating the effects of glycerol and xylitol on human epidermal keratinocytes. The polyols (identical osmolarities; xylitol: 0.0045%-0.45%; glycerol: 0.0027%-0.27%) did not alter cellular viability or intracellular calcium concentration. However, they exerted differential effects on the expression of certain genes and signalling pathways. Indeed, both polyols up-regulated the expression of filaggrin, loricrin, involucrin and occludin; yet, xylitol exerted somewhat more profound effects. Moreover, while both polyols stimulated the MAPK pathway, only xylitol induced the activation-dependent translocation of protein kinase Cδ, a key promoter of epidermal differentiation. Finally, in various keratinocyte inflammation models, both polyols (albeit with different efficacies) exerted anti-inflammatory effects. Taken together, these data strongly suggest that glycerol and xylitol differentially modulate expressions of multiple genes and activities of signalling pathways in epidermal keratinocytes. Thus, our findings invite clinical trials to explore the applicability and the impact of a combined glycerol-xylitol therapy in the management of various skin conditions.

No abstract

A neonatal boy presented with ichthyosiform erythroderma, hypotrichosis, recurrent sepsis and skin infections, failure to thrive, constant vomiting and brain abnormalities. He had persistent thrombocytosis, hypoalbunemia and hypernatremia. IgE levels rose at age 0.6 years (985 kU/l) without eosinophilia. Cow milk allergy was diagnosed at 0.7 years. IVIG treatment from 0.6 years reduced infections and acitretin from age 0.7 years reduced scaling. Skin biopsy showed a psoriformic reaction with normal LEKTI but absent filaggrin staining. Vast immunological and metabolic analyses and ichtyosis and immunodeficiency gene panels were normal. Whole exome sequencing showed a heterozygous Desmoplakin missense variant c. 1756C>T, p.(His586Tyr). A heterozygous mutation in the neighboring nucleotide c.1757C>T, p.(His586Pro) with a similar phenotype was reported in one patient. The phenotype is typical for severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome to date reported in five other patients with homozygous Desmoglein 1 mutations. Desmoplakins and desmogleins are key molecules in desmosomes, which are adhesive intercellular junctions crucial in tissues prone to mechanical stress (e.g. skin, heart, gastrointestinal mucosa). Desmosomal proteins play a role in cell signalling and skin barrier function. Reported SAM patients developed dermatitis and erythroderma neonatally with failure to thrive (86%, 6/7), recurrent infections (86%, 6/7), elevated IgE (86%, 6/7), hypotrichosis (71%, 5/7), food allergy (71%, 5/7), developmental delay (71%, 5/7), variable gastrointestinal features (57%, 4/7), hypoalbuminemia (57%, 4/7) and hyper-/hyponatremia (43%, 3/7). The SAM syndrome is clinically similar to Netherton syndrome caused by SPINK5 mutations leading to a severe epidermal barrier defect. Desmoplakin mutations should be included in the differential diagnosis of erythrodermic, allergy and infection prone infants with skin barrier defects. 125Characterization of TSG-6 protein in healthy and inflammatory models of reconstructed human epidermis C Evrard, E De Vuyst, E Faway, C Lambert de Rouvroit, B Flamion and Y Poumay University of Namur, Namur, Belgium TSG-6 is an anti-inflammatory hyaluronan-binding protein involved in extracellular matrix remodelling whose functions have never been studied in skin. Characterization of TSG-6 was carried out in vivo in healthy human epidermis and in vitro using keratinocyte monolayers and reconstructed human epidermis (RHE). Distribution of TSG-6 protein was highlighted by immunofluorescence and levels of relative mRNA and protein expression were respectively measured by RT-qPCR and ELISA. The immunofluorescent signal of TSG-6 protein was located in the living layers of epidermis in vivo and in vitro, mostly in basal keratinocytes, and was restricted to the intracellular compartment. Because the localization of hyaluronan (HA) is in the extracellular matrix, no colocalization of TSG-6 and HA could thus be detected. ELISA assay shows that TSG-6 is abundant in the intracellula...