No abstract

We previously reported a positive feedback loop between S100A8/A9 and proinflammatory cytokines mediated by extracellular matrix metalloproteinase inducer, an S100A9 receptor. Here, we identify neuroplastin-β as an unreported S100A8 receptor. Neuroplastin-β and extracellular matrix metalloproteinase inducer form homodimers and a heterodimer, and they are co-localized on the surface of cultured normal human keratinocytes. Knockdown of both receptors suppressed cell proliferation and proinflammatory cytokine induction. Upon stimulation with S100A8, neuroplastin-β recruited GRB2 and activated extracellular signal-regulated kinase, resulting in keratinocyte proliferation. Keratinocyte proliferation in response to inflammatory stimuli was accelerated in involucrin promoter-driven S100A8 transgenic mice. Further, S100A8 and S100A9 were strongly up-regulated and co-localized in lesional skin of atopic dermatitis patients. Our results indicate that neuroplastin-β and extracellular matrix metalloproteinase inducer form a functional heterodimeric receptor for S100A8/A9 heterodimer, followed by recruitment of specific adaptor molecules GRB2 and TRAF2, and this signaling pathway is involved in activation of both keratinocyte proliferation and skin inflammation in atopic skin. Suppression of this pathway might have potential for treatment of skin diseases associated with chronic inflammation such as atopic dermatitis.

Trichophyton interdigitale and T. rubrum are anthropophilic species that are most frequently isolated from tinea unguium, tinea pedis and tinea corporis worldwide. 1,2 Terbinafine (TRF) has been used in the treatment of these infections for more than 20 years. Recently, TRF-resistant strains were isolated from human patients. [3][4][5][6] Indeed, patients with tinea unguium and tinea pedis remain uncured or become re-infected, suggesting that antifungal drug-resistant strains might be emerging in Japan. 6 We expect that the prevalence of foot dermatophytosis due to antifungal drug-resistant strains will increase in Japanese patients. However, an epidemiological study of TRF-resistant strains in Japanese patients has not yet been conducted.In the present study, antifungal susceptibility testing was performed on clinical isolates from Japanese patients to assess TRF resistance patterns of T. interdigitale and T. rubrum strains.Moreover, we sequenced the squalene epoxidase (SQLE) encoding gene of TRF-resistant T. rubrum strains. TRF is known to target the SQLE enzyme in dermatophytes. Yamada et al. reported missense

In this review, we summarize the status of Trichophyton tonsurans infection in Japan in terms of epidemiology, clinical features, diagnosis and infection control. Since approximately 2000, outbreaks of T. tonsurans infections among combat sports club members have been reported frequently, with the infection then spreading to their friends and family members. The most common clinical features of T. tonsurans infection are tinea corporis, which is difficult to differentiate from eczema, and tinea capitis. Tinea capitis is classified as the seborrheic form, kerion celsi form or "black dot" form, although 90% or more of patients are asymptomatic carriers. The diagnosis of symptomatic T. tonsurans infection is established by potassium hydroxide examination and fungal culture. However, because there are many asymptomatic carriers of T. tonsurans infection, tests using the hairbrush culture method are necessary. An increase in asymptomatic carriers of T. tonsurans makes assessment of the current prevalence of the infection challenging and underscores the importance of educational efforts and public awareness campaigns to prevent T. tonsurans epidemics.

Mammalian epidermis is a stratified epithelium composed of distinct layers of keratinocytes. The outermost cornified layer is a primary barrier that consists of a cornified envelope, an insoluble structure assembled by cross-linked scaffold proteins, and a surrounding mixture of lipids. Skin keratinocytes undergo a multistep differentiation process, but the mechanism underlying this process is not fully understood. We demonstrate that the transcription factor MafB is expressed in differentiating keratinocytes in mice and is transcriptionally upregulated upon human keratinocyte differentiation in vitro. In MafB-deficient mice, epidermal differentiation was partially impaired and the cornified layer was thinner than in wild-type mice. On the basis of transcriptional profiling, we detected reduced expression levels of a subset of cornified envelope genes, for example, filaggrin and repetin, in the MafB(-/-) epidermis. By contrast, the expression levels of lipid metabolism-related genes, such as Alox12e and Smpd3, increased. The upregulated genes in the MafB(-/-) epidermis were enriched for putative target genes of the transcription factors Gata3, Grhl3, and Klf4. Immunohistochemical analysis of skin biopsy samples revealed that the expression levels of filaggrin and MafB were significantly reduced in patients with human atopic dermatitis and psoriasis vulgaris. Our results indicate that MafB is a component of the gene expression program that regulates epidermal keratinocyte differentiation.