The IL17F His161Arg polymorphism, a potential risk locus for psoriasis, increases serum levels of interleukin-17F in an Asian population.

Interleukin 17 (IL-17) plays pivotal role in the pathogenesis of psoriasis. In a previous study, we identified a locus in the IL17F gene that is associated with psoriasis, the IL17F rs763780 (His161Arg) T/C variant. The current study aimed to elucidate the association between this polymorphism and psoriasis, and to determine its effect on serum levels of cytokine. A total of 116 psoriasis patients and 97 healthy volunteers were recruited. Genotyping analysis was performed using quantitative polymerase chain reaction, and serum levels of cytokine were measured using a multiplex immunoassay. The IL17F His161Arg polymorphism was significantly associated with psoriasis based on the genotype and allele analyses. Psoriasis patients harbouring the mutant allele had significantly increased serum levels of IL-17F. Our results suggest that this polymorphism is a potential risk locus for psoriasis and that it results in a direct increase in IL-17F production.

Total serum immunoglobulin E level and specific allergens in adults with skin diseases.

BACKGROUND: Immunoglobulin E (IgE) plays an important role in allergic diseases. Although several studies have shown the association of serum total IgE and allergen-specific IgE levels with allergic dermatological diseases such as atopic dermatitis, there are few studies addressing this association for skin diseases in general. AIMS: We sought to evaluate IgE levels in skin diseases and investigate the differences based on the disease type and clinical factors such as gender and age. METHODS: Data from 2836 patients who visited the dermatologic clinic of the Konkuk University Hospital, Seoul, Republic of Korea for 4 years were reviewed to document IgE levels and clinical information. IgE levels were collated with the type of skin disease, gender, and age. RESULTS: Patients with atopic dermatitis had a much higher total IgE level and were more susceptible to allergens as compared to other disease groups. Patients in other disease groups showed no significant differences in IgE levels. Men showed higher total IgE levels but the gender differences decreased with increasing age. LIMITATIONS: The data were collected from patients at a referral centre and thus may not represent the general population of dermatologic patients. There was a lack of information regarding factors that could potentially influence IgE levels such as smoking history and disease severity. CONCLUSIONS: The results suggest that there are physiological or environmental differences in IgE-mediated immune responses between males and females. Also, except for atopic dermatitis, there were no clinical differences in the IgE levels among various skin diseases.

Arctiin regulates collagen type 1α chain 1 mRNA expression in human dermal fibroblasts via the miR­378b­SIRT6 axis.

Arctiin, a lignin isolated from Arctium lappa, exhibits a variety of biological effects, including anti­viral, anti­inflammatory, and anti­proliferative actions, in mammalian cells. In a previous study, arctiin was demonstrated to induce procollagen type I synthesis and exhibited protective effects against ultraviolet B (UVB) radiation in normal human dermal fibroblasts (nHDFs). However, the underlying molecular mechanism of arctiin­mediated collagen synthesis remains unknown. In the present study, the mechanism for increased expression of collagen type 1α 1 chain (COL1A1) mRNA in arctiin­induced nHDFs was identified. The expression of microRNA­378b (miR­378b), downregulated by arctiin, was correlated with the expression of sirtuin­6 (SIRT6) mRNA, a regulator of COL1A1 mRNA. Furthermore, it was revealed that arctiin protected the UVB radiation­mediated decrease in COL1A1 mRNA expression, through the miR­378b/SIRT6 signaling pathway. In conclusion, these results suggest that arctiin regulates COL1A1 through the miR­378b­SIRT6 axis.

MicroRNA­378b regulates α­1­type 1 collagen expression via sirtuin 6 interference.

Ultraviolet (UV) light mediates skin aging and induces destruction of the dermis by modulating the expression levels of extracellular matrix­associated genes, including collagen and matrix metalloproteinases. Sirtuin 6 (SIRT6), a member of the sirtuin family of proteins, regulates collagen metabolism and is an established anti­aging protein. However, the exact underlying mechanism by which SIRT6 expression is regulated in dermal fibroblasts during the aging process is unclear. The present study demonstrated that expression of microRNA­378b (miR­378b) is induced in UVB­exposed human dermal fibroblasts (HDFs), and this was inversely associated with the mRNA expression levels of α­1­type 1 collagen (COL1A1). In addition, knockdown of miR­378b enhanced the mRNA expression levels of COL1A1 in HDFs. A target analysis for miR­378b was performed, and the results revealed that SIRT6, a regulator of COL1A1, contains a target sequence for miR­378b in its 3'untranslated region. Notably, the present study demonstrated that an miR­378b mimic and inhibitor may directly regulate SIRT6 expression in HDFs. In conclusion, the present study suggested that miR­378b represses the mRNA expression levels of COL1A1 via interference with SIRT6 in HDFs, and may contribute to the underlying molecular mechanism by which UVB inhibits collagen I in dermal fibroblasts.

Assessment of Arterial Stiffness in Korean Patients With Psoriasis by Cardio-Ankle Vascular Index.

Many recent studies have suggested that psoriasis, a chronic, inflammatory, immune-mediated skin disease, is associated with increased risk of cardiovascular disease (CVD). We aimed to compare arterial stiffness in psoriasis and control patient groups using the cardio-ankle vascular index (CAVI) and to determine whether psoriasis is an independent risk factor for CVD. A total 103 patients with psoriasis and 103 age- and sex-matched controls were enrolled. Compared with controls, the patients showed a higher CAVI ( P = .03), particularly patients older than 40 years. The duration of psoriasis exhibited a positive correlative tendency with CAVI ( P = .066). Moreover, psoriasis is an independent predictor of arterial stiffness after adjusting for other factors ( P = .011). We suggest that psoriasis can be a risk factor for CVD, and older patients with psoriasis of longer disease duration should be monitored carefully for cardiovascular risk.

Pretreatment of Ferulic Acid Protects Human Dermal Fibroblasts against Ultraviolet A Irradiation.

BACKGROUND: Approximately 90%~99% of ultraviolet A (UVA) ray reaches the Earth's surface. The deeply penetrating UVA rays induce the formation of reactive oxygen species (ROS), which results in oxidative stress such as photoproducts, senescence, and cell death. Thus, UVA is considered a primary factor that promotes skin aging. OBJECTIVE: Researchers investigated whether pretreatment with ferulic acid protects human dermal fibroblasts (HDFs) against UVA-induced cell damages. METHODS: HDF proliferation was analyzed using the water-soluble tetrazolium salt assay. Cell cycle distribution and intracellular ROS levels were assessed by flow cytometric analysis. Senescence was evaluated using a senescence-associated ß-galactosidase assay, while Gadd45α promoter activity was analyzed through a luciferase assay. The expression levels of superoxide dismutase 1 (SOD1), catalase (CAT), xeroderma pigmentosum complementation group A and C, matrix metalloproteinase 1 and 3, as well as p21 and p16 were measured using quantitative real-time polymerase chain reaction. RESULTS: Inhibition of proliferation and cell cycle arrest were detected in cells that were irradiated with UVA only. Pretreatment with ferulic acid significantly increased the proliferation and cell cycle progression in HDFs. Moreover, ferulic acid pretreatment produced antioxidant effects such as reduced DCF intensity, and affected SOD1 and CAT mRNA expression. These effects were also demonstrated in the analysis of cell senescence, promoter activity, expression of senescent markers, and DNA repair. CONCLUSION: These results demonstrate that ferulic acid exerts protective effects on UVA-induced cell damages via anti-oxidant and stress-inducible cellular mechanisms in HDFs.

Pedunculated Nodules as a Variant of Dermatofibrosarcoma Protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a rare disease of dermal fibroblastic origin that accounts for less than 5% of all soft tissue sarcomas in adults. DFSP grows slowly and is an asymptomatic lesion at the initial diagnosis. Herein, we report a case of multiple pedunculated nodules as a variant of DFSP. A 47-year-old man presented with a 7-month history of multiple well-circumscribed, firm, pedunculated nodules on the inguinal area. Histopathologic examination results showed densely packed uniform spindle cells with a storiform and cartwheel pattern, and positivity for CD34. Wide excision and skin graft were performed and at the 6-month follow-up, there was no evidence of recurrence or metastasis.