ABSTRACT
BACKGROUND: Alopecia areata (AA) is an autoimmune skin disease difficult to manage and treat. The pathogenesis of AA features a T-cell-associated autoimmune process, and systemic immunosuppressive therapy is prescribed widely for AA. OBJECTIVE: To evaluate the efficacy and tolerance of systemic low-dose methotrexate (LD-MTX) therapy in treatment of recalcitrant AA multiplex. METHODS: In a retrospective, non-controlled study, we evaluated 29 patients with recalcitrant AA treated with LD-MTX and assessed the therapeutic response according to severity of disease, disease duration, cumulative dose of MTX, and drug safety. RESULTS: MTX was administered twice weekly, and the mean maximum weekly dose was 14.48 mg. The response was A5 (regrowth=100.0%) in 14 (48.3%) patients and A4 (regrowth of 75%~90%) in 12 (41.4%) patients. Three patients had poor response to LD-MTX treatment (A2: n=2 [6.9%], A1: n=1 [3.4%]). All three of the patients showing a poor response had disease durations exceeding 24 months. Relapse was observed in 31% of patients with more than 75% regrowth. Common side-effects were elevated liver enzyme levels and gastrointestinal discomfort. CONCLUSION: LD-MTX appears to be an effective and well-tolerated treatment for recalcitrant AA multiplex.
Subject(s)
Humans , Alopecia Areata , Alopecia , Liver , Methotrexate , Recurrence , Retrospective Studies , Skin DiseasesABSTRACT
BACKGROUND: Interleukin-17A (IL-17A) is mainly secreted from Th17 cells that are activated by various stimuli including CpG oligodeoxynucleotide, a Toll-like receptor 9 (TLR9) ligand. Recently, it has been demonstrated that keratinocytes play an important role in the pathogenesis of psoriasis. OBJECTIVE: To investigate the potential role of keratinocytes, we examined whether TLR9 ligand CpG induces IL-17A expression in keratinocytes. METHODS: We used HaCaT keratinocytes as a model system, and determined CpG-induced IL-17A using enzyme-linked immunosorbent assay and Western blot. RESULTS: When HaCaT keratinocytes were treated with CpG, the expression of several cytokines including IL-17A, tumor necrosis factor-α and CCL20 was markedly increased. Treatment with nuclear factor (NF)-κB inhibitor significantly blocked the CpG-induced IL-17A production, indicating that CpG induced IL-17A expression through the NF-κB signaling pathway. In addition, IL-17A secreted from keratinocytes stimulated the CD4⁺ T cells, resulting in strong induction of IL-22 production. CONCLUSION: Since IL-22 is an important mediator for psoriatic inflammation, our data suggest that keratinocytes can participate in the pathogenesis of psoriasis via the TLR9-dependent IL-17A production.
Subject(s)
Blotting, Western , Cytokines , Enzyme-Linked Immunosorbent Assay , Inflammation , Interleukin-17 , Keratinocytes , Necrosis , Psoriasis , T-Lymphocytes , Th17 Cells , Toll-Like Receptor 9ABSTRACT
MIDAS syndrome (microphthalmia-dermal aplasia-sclerocornea) is an X-linked dominant genetic disease. In most patients, the unbalanced translocation or deletion of the X chromosome short-arm 22.3 band is observed. This disease characteristically presents as linear atrophy of the skin limited to the face and neck, accompanied by congenital eye disease. A 9-month-old female who had linear skin atrophy on the right side of her chin visited our clinic. She also presented with microphthalmia and sclerocornea on her right eye. Results of a chromosomal study revealed a deletion of the X-chromosome short-arm 22.31 band. Here, we report on this MIDAS syndrome patient with linear skin atrophy on the face.
Subject(s)
Female , Humans , Infant , Atrophy , Chin , Eye Diseases , Microphthalmos , Neck , Skin , X ChromosomeABSTRACT
O-linked beta-N-acetylglucosamine modification is an important post-translational modification, emerging as a novel regulatory mechanism in various cellular events. Recently, several studies have shown that O-GlcNAcylation plays an essential role in human breast, lung, and colon cancers. With regard to skin cancers, the role of O-GlcNAcylation has yet to be elucidated. To investigate whether O-GlcNAcylation is linked to human skin tumor development, immunohistochemical analysis was performed to investigate the presence of O-GlcNAcylation in various skin tumors. We evaluated the levels of O-GlcNAcylation, O-GlcNAc transferase, and O-GlcNAcase in 29 benign tumors, 12 premalignant tumors, and 26 malignant tumors in skin. Compared to the benign tumors, premalignant and malignant tumors had increased patterns of O-GlcNAcylation. In addition, the O-GlcNAc transferase and O-GlcNAcase levels were higher in premalignant and malignant tumors than in benign tumors. Interestingly, O-GlcNAcase levels were significantly increased in premalignant tumors compared to benign and malignant tumors. These results suggest that O-GlcNAcylation of proteins may play an important role in the development of human skin tumors.
Subject(s)
Humans , Breast , Colonic Neoplasms , Immunohistochemistry , Lung , Protein Processing, Post-Translational , Skin Neoplasms , Skin , TransferasesABSTRACT
Skin is the outermost organ and acts as a barrier between the organism and environment. Skin protects the organism from environmental insults, such as chemicals, pathogens, and UV light. Much of the protective function of skin is dependent on the epidermis, a multi-layered epithelium that is composed of various cell types such as keratinocytes and melanocytes. Keratinocytes produce protective components through a sophisticated differentiation process. Disturbance of keratinocyte differentiation is related to several skin diseases such as psoriasis and atopic dermatitis. In this study, we prepared extract of combined medicinal plants (ECMP) consisting of Taraxacum platycarpum H. Dahlstedt, Heartleaf Houttuynia, Glycyrrhiza uralensis Fischer, and root bark of Ulmus davidiana. We demonstrated that ECMP enhanced keratinocyte differentiation and barrier functionality using an in vitro cell culture system and in vivo animal test. Treatment of cultured keratinocytes with ECMP resulted in induction of keratinocyte differentiation, as evidenced by increased differentiation markers such as involucrin, loricrin, and filaggrin. In line with these results, ECMP decreased proliferation of keratinocytes cultured in vitro. ECMP applied topically to tape-stripped mouse skins accelerated reduction of transepidermal water loss (TEWL), indicating fast recovery of barrier function. Immunohistochemistry showed that ECMP increased the filaggrin level in tape-stripped mouse skins. These results suggest that ECMP may be applicable for keratinocyte differentiation-related skin diseases.
Subject(s)
Animals , Mice , Antigens, Differentiation , Cell Culture Techniques , Dermatitis, Atopic , Epidermis , Epithelium , Glycyrrhiza uralensis , Houttuynia , Immunohistochemistry , Keratinocytes , Melanocytes , Plants, Medicinal , Psoriasis , Skin , Skin Diseases , Taraxacum , Ulmus , Ultraviolet RaysABSTRACT
It has been reported that the levels of erythropoietin are associated with diabetes mellitus. Glomerular epithelial cells, located in the renal cortex, play an important role in the regulation of kidney function and hyperglycemia-induced cell loss of glomerular epithelial cells is implicated in the onset of diabetic nephropathy. This study investigated the effect of high glucose on erythropoietin and erythropoietin receptor expression in rat glomerular epithelial cells. We found that 25 mM D-glucose, but not mannitol or L-glucose, stimulated erythropoietin mRNA and protein expression in a time dependent manner (>4 h) in rat glomerular epithelial cells. In addition, 25 mM glucose, but not mannitol or L-glucose, also increased the phosphorylation of erythropoietin receptor, suggesting a role for erythropoietin receptor phosphorylation in erythropoietin synthesis. We conclude that high glucose stimulates erythropoietin production and erythropoietin receptor phosphorylation in rat glomerular epithelial cells.