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Human Skin Cells (human + skin_cell)
Selected AbstractsRegulation of 1-,, 25-Dihydroxyvitamin D3 on Interleukin-6 and Interleukin-8 Induced by Sulfur Mustard (HD) on Human Skin Cells,BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2003Carmen M. Arroyo Stimulation of human skin fibroblasts with sulfur mustard (10,4 M for 24 hr at 37°) resulted in approximately a 5 times increase in the secretion of interleukin-6 and over a 10 times increase for interleukin-8, which was inhibited by 1-,, 25 (OH)2D3, at ,10,9 M. 1-,, 25 (OH)2D3 also suppressed interleukin-8 secretion by 5 times and interleukin-6 by 4 times on sulfur mustard-stimulated human epidermal keratinocytes at concentrations , 10,9 M. The effect of 1-,, 25 (OH)2D3 was dose-dependent for the suppression of interleukin-6 and interleukin-8 induced by sulfur mustard on human skin fibroblasts/human epidermal keratinocytes, apparent at nanomolar concentrations. Our results indicate that the suppression of these inflammatory mediators by 1-,, 25 (OH)2D3 is dependent on the source of the primary cultures, cell densities, and kinetics of pretreatments. In contrast to the inhibition of cytokine/chemokine production, cell proliferation was enhanced by almost 1.7 times on treated human epidermal keratinocytes with 1-,, 25 (OH)2D3 (1×10,9 M) after sulfur mustard-stimulation (10,4 M for 24 hr at 37°C). The observed enhancement diversified based on cell density, and kinetics of pretreatment with a maximal synergism (s) observed at 1×10,9 M. Photomicrographs show typical signs of cellular degeneration caused by sulfur mustard such as chromatin condensation. The observed cellular degeneration was lessened when human epidermal keratinocytes were treated with 1-,, 25 (OH)2D3 (2×10,9 M). 1-,, 25(OH)2D3 could be an alternative treatment for cutaneous inflammation disorders caused by sulfur mustard because we have demonstrated its ability to suppress inflammatory mediators and enhanced cell proliferation in human skin cells stimulated with sulfur mustard. [source] Water soluble fraction of solar-simulated light-exposed crude oil generates phosphorylation of histone H2AX in human skin cells under UVA exposureENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2007Yuko Ibuki Abstract Crude oil contains compounds, which have toxic and cancer-causing properties to humans. The oil spilled in environments is usually exposed to sunlight; however, the toxicity of sunlight-exposed oil is poorly understood. In this study, we found that the water soluble fraction (WSF) of crude oil irradiated with solar-simulated light (SSL) generated phosphorylation of histone H2AX (,-H2AX) in human skin cells under UVA irradiation, which was due to the formation of DNA double strand breaks (DSBs). Crude oil was exposed to SSL for ,7 days. The WSF obtained from unexposed crude oil showed no toxicity, whereas the WSF obtained from crude oil pre-exposed to SSL induced acute cell death on exposure to UVA irradiation (induction of phototoxicity), which was more remarkable in human skin fibroblasts than human skin keratinocytes. ,-H2AX was detected in both cell lines immediately after treatment with the WSF plus UVA. Interestingly, ,-H2AX was detectable even at low SSL- and UVA-doses, which induced no cytotoxicity. The WSF of crude oil irradiated with SSL, generated DSBs under UVA irradiation, which were detected by biased sinusoidal field gel electrophoresis. This was confirmed using xrs-5 cells isolated from CHO-K1 cells, which are deficient in a repair enzyme for DSBs; the WSF plus UVA induced a more dramatic decrease in survival in xrs-5 cells than CHO-K1 cells. These findings demonstrate that exposure of crude oil to sunlight makes the WSF phototoxic, generating DSBs accompanying the appearance of ,-H2AX in human skin cells. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc. [source] 20-O-,-D-Glucopyranosyl-20 (S)-protopanaxadiol (compound K) induces expression of hyaluronan synthase 2 gene in transformed human keratinocytes and fibroblasts and increases hyaluronan in hairless mouse skinINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2004S. Kim Ginsenosides, the major active ingredient of ginseng, show a variety of biomedical efficacies such as anti-aging, anti-oxidation and anti-inflammatory activities. To understand the effects of 20-O-,-D-glucopyranosyl-20 (S)-protopanaxadiol (compound K), one of the major metabolites of ginsenosides on the skin, we assessed the expression level of approximately 100 transcripts in compound K-treated HaCaT cells using cDNA microarray analysis. Compound K treatment induced differential expression of 40 genes, which have been reported to be involved in the organization of the structure of the extracellular matrix as well as defense responses in human skin cells. One of the most interesting findings is a two-fold increase in hyaluronan synthase2 (HAS2) gene expression by compound K. We found that change in expression of HAS2 gene represents a specific response of HaCaT cells to compound K because hyaluronan synthase 1,3 was not changed by treatment with compound K. We also demonstrated that the compound K effectively induced hyaluronan synthesis in human skin cells and hairless mouse skin. A human clinical study indicated that topical application of compound K containing oil-in-water emulsion showed improvement of xerosis, wrinkle and fine lines in the aged skin. We concluded that compound K has anti-aging effects by the induction of HAS2 gene expression and following hyaluronan synthase. [source] Improving cellular function through modulation of energy metabolismINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2004D. Maes The ambivalent consequences of mitochondrial stimulation on cellular activity have been well established. Mitochondria supply the cell with energy through a process of oxidative phosphorylation but thereby generate free radicals, resulting in the accumulation of hydrogen peroxide in the cytoplasm. We have investigated the impact of cellular senescence as well as UV irradiation, on the balance between these two activities. The adenosine triphosphate (ATP) level, DNA and protein synthesis in fibroblasts obtained from donors between 30 and 90 years of age appeared to be significantly influenced by the aging process. Both DNA and protein synthesis could be stimulated by increasing intracellular ATP levels. In-vitro senescent fibroblasts showed a reduction in the level of ATP as well as a shift in mitochondrial membrane potential. At the same time, there was an increase in intracellular hydrogen peroxide with increasing population doubling, indicating a clear dysfunction of the metabolic machinery in the mitochondria of senescent cells. To counteract this degradation of the energy pool, we treated cells with creatine, which is known to restore the pool of phosphocreatine in the mitochondria. Creatine treatment significantly increased cell survival after UV exposure, stimulated the repair of UVB-induced DNA damage in keratinocytes and caused a significant reduction in the number of sunburn cells in a UVB-exposed reconstituted skin model. These results clearly indicate that restoration of the energy pool in mitochondria increased cellular self-defense mechanism. These data show the important role played by the mitochondrial energy metabolism on the aging process, and indicate a possible therapy that can be used to counteract this negative effect. Treatment with creatine seems to provide the necessary boost to the cellular metabolism, which leads to an induction of a significant amount of protection and repair to human skin cells. [source] A preliminary examination of the role of NFAT 3 in human skin, cultured keratocytes and dermal fibroblastsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2010Wael I. Al-Daraji Background: Ciclosporin A (CsA) is widely utilized for the treatment of inflammatory skin diseases such as psoriasis. The therapeutic effects of CsA are thought to be mediated via its immunosuppressive action on infiltrating lymphocytes in skin lesions. CsA and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). Methods: RT-PCR and Western Analysis were used to investigate the presence of NFAT-3 mRNA and protein in human keratocytes. Tissue culture of human keratocytes and immunostaining of cells on coverslips and confocal microscopy were used to assess the degree of nuclear localisation of NFAT-3 in cultured cells. Keratome biopsies were taken from patients with psoriasis (lesional and non-lesional skin) and normal skin and immunohistochemistry was used to assess the NFAT-3 localisation in these biopsies using a well characterized anti-NFAT-3 antibody. Results: The NFAT-3 mRNA and protein expression was demonstrated using RT-PCR and Western blotting. The expression of NFAT-3 in human keratocytes and response to different agonists provides perhaps a unique opportunity to examine the regulation, subcellular localization and kinetics of translocation of different NFATs in primary cultured human cells. As with NFAT 1, NFAT 2 and recently NFAT 5, differentiation-promoting agents that increase intracellular calcium concentration induced nuclear translocation of NFAT-3 in cultured keratocytes but with different kinetics. Conclusion: These data provide the first evidence of that NFAT-3 is expressed in normal skin, psoriasis and that NFAT-3 functionally active in human keratocytes and that nuclear translocation of NFAT-3 in human skin cells has different kinetics than NFAT 1 suggesting that NFAT-3 may play an important role in regulation of keratocytes proliferation and differentiation at a different stage. Inhibition of this pathway in human epidermal keratocytes many account, in part for the therapeutic effects of CsA and tacrolimus in skin disorders such as psoriasis. Al-Daraji WI. A preliminary examination of the role of NFAT 3 in human skin, cultured keratocytes and dermal fibroblasts. [source] Total body exposure to ultraviolet radiation does not influence plasma levels of immunoreactive ,-endorphin in manPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 6 2001Marjolein Wintzen Background/Aims: A growing number of reports support evidence of proopiomelanocortin (POMC)-derived peptides in human skin cells, although not consistently. Also the effect of ultraviolet radiation (UVR) on cutaneous and plasma levels of these POMC peptides has not been established unequivocally. We hypothesized that production of ,-endorphin (,E) may explain the sense of well-being many people experience when sun-bathing. The aim of the present study was to investigate whether exposure of the skin to UVR elevates plasma ,E. Method: Healthy volunteers (n=26) received a single, weighted dose of 15 J/cm2 of UVA. Several times during the hour following irradiation, plasma ,E- immunoreactivity (,E-IR) was determined by radioimmunoassay. The effect of repeated exposure wasassessed in 35 patients treated with UVB, UVA, or UVA-1. Plasma ACTH-IR was monitored in parallel. Results: Overall, plasma levels of ,E-IR and ACTH-IR showed no significant changes during the experiment, indicating that these peptides are not influenced by single or repeated exposures to UVR of different wavelengths. Conclusion: On the basis of these results, the skin does not appear to contribute significantly to the levels of circulating ,E or ACTH. These data offer no support for the hypothesis that exposure to UVR leads to an increased concentration of circulating ,E, which could contribute to the feeling of well-being that often accompanies sun-bathing. [source] Characterization of Ninjurin and TSC22 induction after X-irradiation of normal human skin cellsTHE JOURNAL OF DERMATOLOGY, Issue 1 2008Manabu KOIKE ABSTRACT The skin is an external organ that is most frequently exposed to radiation. It is important to elucidate the influence of radiation exposure on the skin at the molecular level. To identify radiation-responsive genes in human skin cells, we used microarray technology to examine the effects of irradiation on 641 genes in normal human epidermal keratinocytes at 4 h and 8 h postirradiation with a cytotoxic dose of X-ray (10 Gy). We found that 18 genes were upregulated and 35 genes were downregulated in keratinocytes at 4 h and/or 8 h postirradiation. Ninjurin, whose function remains unknown in keratinocytes, was induced most strongly by X-irradiation. Several known apoptosis-related genes, such as TSC22, were also upregulated. We characterized Ninjurin and TSC22 induction after X-irradiation of normal human skin cells. The induction of the expression of Ninjurin and TSC22 mRNA in keratinocytes following high-dose X-irradiation was confirmed by northern blot analysis. In dermal fibroblasts, Ninjurin, but not TSC22, was induced after X-ray irradiation. The dependence of both gene expression on the status of an apoptosis regulator, p53, was found. In addition, the expression of both mRNA was induced upon treatment with an apoptosis inducer, etoposide. On the other hand, TSC22, but not Ninjurin, was induced and accumulated in keratinocytes upon treatment with an apoptosis inducer, anisomycin. However, in transient expression assay, EYFP-TSC22, as well as EYFP-Ninjurin or EYFP alone, did not induce apoptosis in keratinocytes in contrast to EYFP-GADD45. Taken together, these findings have important implications on the understanding of the mechanism underlying the complex response of skin cells following X-irradiation. [source] Regulation of 1-,, 25-Dihydroxyvitamin D3 on Interleukin-6 and Interleukin-8 Induced by Sulfur Mustard (HD) on Human Skin Cells,BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2003Carmen M. Arroyo Stimulation of human skin fibroblasts with sulfur mustard (10,4 M for 24 hr at 37°) resulted in approximately a 5 times increase in the secretion of interleukin-6 and over a 10 times increase for interleukin-8, which was inhibited by 1-,, 25 (OH)2D3, at ,10,9 M. 1-,, 25 (OH)2D3 also suppressed interleukin-8 secretion by 5 times and interleukin-6 by 4 times on sulfur mustard-stimulated human epidermal keratinocytes at concentrations , 10,9 M. The effect of 1-,, 25 (OH)2D3 was dose-dependent for the suppression of interleukin-6 and interleukin-8 induced by sulfur mustard on human skin fibroblasts/human epidermal keratinocytes, apparent at nanomolar concentrations. Our results indicate that the suppression of these inflammatory mediators by 1-,, 25 (OH)2D3 is dependent on the source of the primary cultures, cell densities, and kinetics of pretreatments. In contrast to the inhibition of cytokine/chemokine production, cell proliferation was enhanced by almost 1.7 times on treated human epidermal keratinocytes with 1-,, 25 (OH)2D3 (1×10,9 M) after sulfur mustard-stimulation (10,4 M for 24 hr at 37°C). The observed enhancement diversified based on cell density, and kinetics of pretreatment with a maximal synergism (s) observed at 1×10,9 M. Photomicrographs show typical signs of cellular degeneration caused by sulfur mustard such as chromatin condensation. The observed cellular degeneration was lessened when human epidermal keratinocytes were treated with 1-,, 25 (OH)2D3 (2×10,9 M). 1-,, 25(OH)2D3 could be an alternative treatment for cutaneous inflammation disorders caused by sulfur mustard because we have demonstrated its ability to suppress inflammatory mediators and enhanced cell proliferation in human skin cells stimulated with sulfur mustard. [source] Cytotoxicity of lavender oil and its major components to human skin cellsCELL PROLIFERATION, Issue 3 2004A. Prashar Concerns are building about the potential for irritant or allergenic skin reactions with the use of lavender oil. This study has demonstrated that lavender oil is cytotoxic to human skin cells in vitro (endothelial cells and fibroblasts) at a concentration of 0.25% (v/v) in all cell types tested (HMEC-1, HNDF and 153BR). The major components of the oil, linalyl acetate and linalool, were also assayed under similar conditions for their cytotoxicity. The activity of linalool reflected that of the whole oil, indicating that linalool may be the active component of lavender oil. Linalyl acetate cytotoxicity was higher than that of the oil itself, suggesting suppression of its activity by an unknown factor in the oil. Membrane damage is proposed as the possible mechanism of action. [source] A Photoactivated trans -Diammine Platinum Complex as Cytotoxic as CisplatinCHEMISTRY - A EUROPEAN JOURNAL, Issue 11 2006Fiona S. Mackay Abstract The synthesis and X-ray structure (as the tetrahydrate) of the platinum(IV) complex trans,trans,trans -[Pt(N3)2(OH)2(NH3)2] 3 are described and its photochemistry and photobiology are compared with those of the cis isomer cis,trans,cis -[Pt(N3)2(OH)2(NH3)2] 4. Complexes 4 and 3 are potential precursors of the anticancer drug cisplatin and its inactive trans isomer transplatin, respectively. The trans complex 3 is octahedral, contains almost linear azide ligands, and adopts a layer structure with extensive intermolecular hydrogen bonding. The intense azide-to-platinum(IV) charge-transfer band of complex 3 (285 nm; ,=19,500,M,1,cm,1) is more intense and bathochromically shifted relative to that of the cis isomer 4. In contrast to transplatin, complex 3 rapidly formed a platinum(II) bis(5,-guanosine monophosphate) (5,-GMP) adduct when irradiated with UVA light, and did not react in the dark. Complexes 3 and 4 were non-toxic to human skin cells (keratinocytes) in the dark, but were as cytotoxic as cisplatin on irradiation for a short time (50 min). Damage to the DNA of these cells was detected by using the "comet" assay. Both trans- and cis -diammine platinum(IV) diazide complexes therefore have potential as photochemotherapeutic agents. [source] | |||||||||||||