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Seborrhoea and acne are exclusively human diseases and sebaceous gland differentiation is species specific. Therefore, fundamental research on human sebaceous cell function and control requires human in vitro models. The human sebocyte culture model, introduced in 1989, has been used in several studies to elucidate sebaceous gland activity and its regulation at the cellular level. Cultured human sebocytes have been shown to preserve important sebocytic characteristics, although they undergo an incomplete terminal differentiation in vitro. In vitro synthesis of free fatty acids without bacterial involvement and marked interleukin 1α expression at the mRNA and protein levels with no further induction by lipopolysaccharides lead to the assumption that human sebocytes may initiate acne lesions by an intrinsic mechanism. Androgens affected sebocyte activity in vitro in a manner dependent on the localization of the sebaceous glands. In vitro stimulation of sebocyte proliferation by androgens could be completely abolished by spironolactone. Cultured sebocytes strongly expressed type 1 5α-reductase and metabolized testosterone to androstenedione, 5α-androstanedione, 5α-dihydrotestosterone, androsterone and 5α-androstanediol, whereas the levels of 5α-reductase activity were probably not feedback regulated. 4,7β-Dimethyl-4-aza-5αcholestan-3-one, a type 1 5α-reductase inhibitor, induced an early, marked down-regulation of 5α-reductase activity in human sebocytes in vitro, while hydrofinasteride, a type 2 inhibitor, required 10³-fold higher concentrations to induce similar effects. Stimulation of sebocyte proliferation by insulin, thyroid-stimulating hormone and hydrocortisone indicates that the hormonal control of the sebaceous gland could be a complex mechanism. Retinoids inhibited sebocyte proliferation in a dose-dependent manner and down-regulated lipid synthesis and sebocyte differentiation in vitro. Isotretinoin was the most potent compound. On the other hand, vitamin A was found essential for sebocyte activity and differentiation in vitro and could be partially substituted by synthetic retinoids. The inhibitory effect of isotretinoin on sebocyte proliferation was barely affected by the presence of vitamin A. The low persistent isotretinoin levels or, more likely, the considerably elevated tretinoin concentrations detected in human sebocytes after treatment with isotretinoin in vitro may be responsible for the inhibitory effect of this compound on sebocyte activity.

UV radiation is a well-known inducer of epidermal pigmentation that is utilized in therapy for vitiligo, one of the skin depigmentation disorders. Although it has been reported that melanocyte stem cells (McSCs) play essential roles in hair pigmentation, the relationship between McSCs and epidermal pigmentation remains unclear. Repetitive UVB irradiation on the dorsal skin of F1 mice of HR-1 × HR/De caused apparent epidermal pigmentation, and it was characterized by increase in the number of melanocytes. Interestingly, differentiation of McSCs into melanoblasts in hair follicles was followed by induction of epidermal melanocyte differentiation. Administration of a neutralizing antibody for Kit receptor that depletes resident melanoblasts could not suppress increased number of melanocytes. UVB irradiation also induced robust expression of Wnt7a as well as Kitl in epidermis, and β-catenin translocation into nucleus in McSCs. Intradermal injection of IWR-1 (inhibitor of Wnt response 1), a chemical inhibitor of β-catenin activation, and small interfering RNA (siRNA) against Wnt7a suppressed increase in the number of epidermal melanocytes. Taken altogether, it was demonstrated that Wnt7a triggered McSCs differentiation through β-catenin activation, and Kitl might induce following migration of melanoblasts to epidermis. These findings will help in developing therapeutic technologies for vitiligo and other pigmentary disorders.

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For the epidemiological surveys and evaluations of therapy, it is essential to evaluate the severity of diseases. There are several reported methods of assessment for acne severity including lesion counting, comparison of the patient's to a photographic standard and comparison of the patient's to a text description. But all of these are based on opinions of specialists. In this study, we attempted to make an evidence-based grading criteria for acne severity, which was expected to yield consents from most dermatologists. The dermatologists consulted classified the global severity of acne patients without any standard and then counted the numbers of eruptions. Three independent expert dermatologists graded the photographs of these patients. We compared the verdicts of the consulted dermatologist and three experienced dermatologists, and analyzed the relationships between these classifications and numbers of eruptions. Our results showed that most of the dermatologists have similar latent recognitions of acne severity. We selected representative photographs as standards, which would contribute to making adjustments for judgments. Global classifications of dermatologists correlated with numbers of inflammatory eruptions (papules plus pustules), but did not with numbers of comedones. The appropriate divisions of inflammatory eruptions of half of the face to decide classifications were: 0-5, "mild"; 6-20, "moderate"; 21-50, "severe"; and more than 50, "very severe".

In healthy individuals, skin integrity is maintained by epidermal stem cells which self-renew and generate daughter cells that undergo terminal differentiation. Despite accumulation of senescence markers in aged skin, epidermal stem cells are maintained at normal levels throughout life. Therefore, skin ageing is induced by impaired stem cell mobilisation or reduced number of stem cells able to respond to proliferative signals. In the skin, existence of several distinct stem cell populations has been reported. Genetic labelling studies detected multipotent stem cells of the hair follicle bulge to support regeneration of hair follicles but not been responsible for maintaining interfollicular epidermis, which exhibits a distinct stem cell population. Hair follicle epithelial stem cells have at least a dual function: hair follicle remodelling in daily life and epidermal regeneration whenever skin integrity is severely compromised, e.g. after burns. Bulge cells, the first adult stem cells of the hair follicle been identified, are capable of forming hair follicles, interfollicular epidermis and sebaceous glands. In addition, -- at least in murine hair follicles -- they can also give rise to non-epithelial cells, indicating a lineage-independent pluripotent character. Multipotent cells (skin-derived precursor cells) are present in human dermis; dermal stem cells represent 0.3% among human dermal foreskin fibroblasts. A resident pool of progenitor cells exists within the sebaceous gland, which is able to differentiate into both sebocytes and interfollicular epidermis. The self-renewal and multi-lineage differentiation of skin stem cells make these cells attractive for ageing process studies but also for regenerative medicine, tissue repair, gene therapy and cell-based therapy with autologous adult stem cells not only in dermatology. In addition, they provide in vitro models to study epidermal lineage selection and its role in the ageing process.

This study has found an association between AD severity and markers of ROS-associated damage, adding weight to the hypothesis that environmentally generated ROS may induce oxidative protein damage in the stratum corneum, leading to the disruption of barrier function and exacerbation of AD.

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