Evaluation of molecules or extracts modulating seborrhea and its consequences, using normal human culture of sebocytes and keratinocytes, skin explants models and in vivo methods: a case study.

Skin produces sebum through sebocytes. Hyper-seborrhea creates conditions for the development of inflamed cutaneous alterations through bacteria colonization triggering dead cell accumulation and pro-inflammatory mediator release. Study of sebum production, its modulation, and its consequences requires complementary in vitro models in order to evaluate the effect of molecules on cell metabolisms. Clinical studies need to be performed to confirm in vitro results. Effects of phenylpropanoids, obtained by elicitation and purification from plant cell culture of Syringa vulgaris (CCSV), were studied on sebocytes, keratinocytes, and explants, all derived from normal human skins. Normal human sebocytes (NHSs) expressed markers such as cytokeratin-7, cytokeratin-4, and perilipin-2 (PLIN-2) (1); the latter being colocalized with lipid droplets. Lipid droplets clearly appeared and their size increased rapidly when lipogenic agents were used. NHS, normal human keratinocytes (NHK), and explants reacted to presence of bacterial fragments which trigger pre-inflammatory mediator release. CCSV reduced lipid storage and release of pre-inflammatory mediators in NHS, NHK and explants. CCSV also reduced P. acnes growth and triggered beta-defensin-2 and cathelicidin synthesis by NHS, two natural antimicrobial peptides. On volunteers, sebum production, inflamed blemishes, and retentional lesions were significantly reduced after 1 month treatment with CCSV.

A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs' disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G (ARSG) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.