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  • 1
    Electronic Resource
    Electronic Resource
    The cytotoxic effect of neonatal lupus erythematosus and maternal sera on keratinocyte cultures is complement-dependent and can be augmented by ultraviolet irradiation (1996)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 135 (1996), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary To elucidate the role of autoantibodies and ultraviolet (UV) exposure in the pathogenesis of the skin lesions in neonatal lupus erythematostis (NLE). keratinocytes were cultured, as the target cells, from a patient with NLE and from a normal neonate. We demonstrated that the expression of nuclear/cytoplasmic Ro/SSA and La/SSB molecules on to the surface of NLE keratinocytes occurred to a much greater extent than that on normal keratinocytes. A dose of 200 ml/cm2 UVB irradiation on NLE keratinocytes induced a 2.5–3-fold increase in Ro/SSA and La/SSB expression compared to non-irradiated cells. Sera derived from both the NLE patient and from his mother exhibited a cytotoxie effect on NLE keratinocytes, but not on control cells, in the presence of complement. Furthermore, the cytotoxieity of the sera was enhanced on UVB-irradiated NLE keratinocytes. whereas it had no cytotoxie efects on UVB-irradiated control cells. This suggests that the abnormal expression of both Ro/SSA and La/SSB on the surface membrane of NLE keratinocytes induces the autoantibodies and complements to injure the cells. This complement-mediated cytotoxic effect can be augmented by UV irradiation, a concept not incompatible with the exacerbation of the skin eruption in sun-exposed skin sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1996.tb01165.x
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  • 2
    Electronic Resource
    Electronic Resource
    Pigmented eccrine poroma with enhanced endothelin-1 expression: implications for mechanism of hyperpigmentation (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 152 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06560.x
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  • 3
    Electronic Resource
    Electronic Resource
    FK506 independently upregulates transforming growth factor β and downregulates inducible nitric oxide synthase in cultured human keratinocytes: possible mechanisms of how tacrolimus ointment interacts with atopic skin (2004)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 151 (2004), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Tacrolimus ointment (FK506) has been used in recent years for the treatment of atopic dermatitis (AD), with favourable results. Most of the therapeutic efficacy of FK506 in AD has been attributed to its immunomodulatory effects on different immune cell types, but its effects on keratinocytes (KCs) have rarely been discussed. Studies have shown that low expression of transforming growth factor (TGF)-β and high expression of nitric oxide synthase (NOS) are implicated in the pathogenesis of AD.Objectives  To investigate the direct effects of FK506 on KCs in terms of TGF-β and inducible NOS (iNOS), and to explore the interactions between TGF-β and iNOS in the KC system.Methods  Cultured human KCs treated with different concentrations of FK506 were used for investigation. The changes in the KC system induced by FK506 were documented in terms of TGF-β and iNOS using enzyme-linked immunosorbent assay and Western blotting techniques, respectively. The gene expression of both TGF-β and iNOS was also determined. A certain amount of tumour necrosis factor (TNF)-α was introduced to mimic atopic skin in vivo.Results  Our results showed that the release of TGF-β was upregulated in FK506-treated KCs, particularly in the presence of TNF-α, while the expression of iNOS was downregulated. The gene expression of iNOS was also downregulated, as shown by reverse transcriptase–polymerase chain reaction analysis. However, the addition of TNF-α did not further downregulate the expression of iNOS protein, suggesting that FK506 may regulate TGF-β and iNOS through different pathways.Conclusions  Our findings indicate that the direct effects of FK506 on KCs probably contribute to its therapeutic efficacy in the treatment of AD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.06109.x
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  • 4
    Electronic Resource
    Electronic Resource
    FK506 promotes melanocyte and melanoblast growth and creates a favourable milieu for cell migration via keratinocytes: possible mechanisms of how tacrolimus ointment induces repigmentation in patients with vitiligo (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Vitiligo is an acquired pigmentary disorder characterized by depigmentation of skin and hair. As the pathogenesis of this disease is still obscure, the treatment of vitiligo has generally been unsatisfactory and often disappointing. Topical tacrolimus (FK506) ointment has recently been added to the armamentarium against this pigmentary disorder. Despite its clinical efficacy, the underlying mechanisms of how topical tacrolimus induces repigmentation in vitiligo have rarely been investigated. As tacrolimus ointment is applied directly to the skin, its impact on keratinocytes (KCs) requires thorough investigation.Objectives  To investigate the effects of FK506 on melanocyte (MC) and melanoblast (MB) growth via KCs.Methods  Cultured MCs and MBs were treated with supernatant of KC cultures conditioned with various concentrations of FK506. The impact of supernatant on MCs and MBs was assessed in terms of its effect on MC/MB proliferation, melanin formation and cell migration. The activities of matrix metalloproteinase (MMP)-2 and MMP-9, known for their influence on cell migration, were evaluated. The concentrations of MC/MB growth factors in the KC supernatant were also determined.Results  Results demonstrated that proliferation of both MCs and MBs was significantly enhanced by FK506-treated KC supernatant. In addition, the concentration of stem cell factor in KC supernatant increased dose-dependently with FK506 treatment. The supernatant from FK506-treated KC culture showed a significant increase in MMP-9 activity.Conclusions  Our study provides in vitro evidence demonstrating that direct interaction between FK506 and KCs creates a favourable milieu for MC growth and migration. Furthermore, our findings provide a possible mechanism explaining how tacrolimus ointment induces repigmentation in patients with vitiligo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06739.x
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  • 5
    Electronic Resource
    Electronic Resource
    Clear cell eccrine porocarcinoma with extensive cutaneous metastasis and peripheral lymphocyte dysfunction (2003)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 149 (2003), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: An 81-year-old woman came to our clinic (Department of Dermatology, Kaohsiung Medical University, Kaohsiung, Taiwan) with multiple erythematous, indurated papules over the left side of her face. Two years earlier, the patient had a skin biopsy done at a similar anatomical area with the histopathological diagnosis of Bowen's disease. After reviewing surgical specimens and confirming no systemic involvement, clear cell eccrine porocarcinoma with extensive cutaneous metastasis has been diagnosed. In addition, the peripheral blood lymphocyte function of the patient was evaluated. The expression of interleukin-2 receptors on lymphocytes after stimulation is abnormal compared with the age-matched normal control and a patient with cutaneous squamous cell carcinoma. This clinical manifestation of eccrine porocarcinoma is exceptional, and lymphocyte dysfunction in this patient has probably contributed to extensive cutaneous metastasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2003.05638.x
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  • 6
    Electronic Resource
    Electronic Resource
    Abnormal Splenic and Thymic IL-4 and TNF-α Expression in MRL-lpr/lpr Mice (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 41 (1995), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The MRL-lpr/lpr and MRL-++ mice were studied for the expression of cytokines in the spleen, lymph node., thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-a expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-++ mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1α, IL-6 and TNF-a in serum than MRL-++ mice. Interestingly, in MRL-lpr/lpr but not MRL-++ mice, the IL-6 concentration in culture supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-l/? were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-++ mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-α expression may predispose the development of autoimmune reactions. The expression of IL-1ß and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1995.tb03548.x
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  • 7
    Electronic Resource
    Electronic Resource
    A novel missense mutation in the COL7A1 gene underlies epidermolysis bullosa pruriginosa (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 29 (2004), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Epidermolysis bullosa (EB) pruriginosa is a subtype of dominant dystrophic EB (DDEB), characterized by severe pruritus and blistering localized to the extensor surface of the extremities. EB pruriginosa exhibits extensive clinical heterogeneity with variable expression and delayed age of onset. Mutations in the COL7A1 gene, especially in glycine residues within Gly-X-Y repeats, have been shown to cause this form of DDEB. Here, we report a novel COL7A1 mutation in a Taiwanese pedigree with EB pruriginosa. Using PCR and direct sequence analysis we have identified a G→T transversion at nucleotide 7097 in exon 92 of COL7A1, converting a glycine residue to valine (G2366V). The mutation resides within a consecutive, uninterrupted stretch of 17 Gly-X-Y residues in the triple-helical domain of type VII collagen. Interestingly, an affected member of this family also displayed elevated IgE levels, previously reported in some patients with this disorder. Our finding further implicates COL7A1 mutation in the pathogenesis of EB pruriginosa and underscores the heterogeneous clinical symptoms of glycine mutations in DDEB.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.2004.01495.x
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  • 8
    Electronic Resource
    Electronic Resource
    Scleromyxoedema with prominent linear eruption and polyclonal gammopathy (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental dermatology 22 (1997), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.1997.tb02637.x
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  • 9
    Electronic Resource
    Electronic Resource
    FK506 inhibits tumour necrosis factor-α secretion in human keratinocytes via regulation of nuclear factor-κB (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Tacrolimus (FK506) ointment has been used for treatment of inflammatory dermatoses with remarkable success. Our previous studies have indicated that direct modulation of tacrolimus on keratinocytes (KCs) may have an impact on its therapeutic effect. The use of monoclonal antibody specific for tumour necrosis factor (TNF)-α has shown efficacy in treating both psoriasis and Crohn disease. Topical tacrolimus has also been shown to be effective for treating cutaneous manifestations of both diseases.Objectives  To explore the effects of FK506 on human KCs in terms of TNF-α secretion and to investigate the regulatory pathway involved.Methods  Ultraviolet (UV) B-irradiated cultured KCs were treated with various concentrations of FK506. At indicated time points after UVB irradiation we determined: (i) the TNF-α concentrations present in the culture supernatants; (ii) the activation and translocation of nuclear factor (NF)-κB in the cell nucleus; and (iii) the protein expressions of IκB kinase (IKK) and IκB in the cell lysates. In addition, a mouse model was used to corroborate our in vitro findings in vivo. More specifically, topical tacrolimus was applied on to mouse skin unilaterally after UVB irradiation. The effects of FK506 on nuclear NF-κB expression of UVB-irradiated mouse skin were determined.Results  Our results showed that FK506 dose-dependently downregulated the secretion of TNF-α from UVB-irradiated KCs. The activation and translocation of NF-κB in UVB-irradiated KCs were also dose-dependently suppressed by FK506. The degradation of IκB induced by UVB was also inhibited by FK506, while no change in IKK expression was noted regardless of UVB and FK506 treatment. Murine skin biopsies showed that nuclear NF-κB expression induced by UVB was inhibited by topical tacrolimus treatment.Conclusions  Our results indicate that FK506 inhibits TNF-α secretion in human KCs via direct regulation of NF-κB. This modulatory effect of FK506 on KCs offers a possible mechanism for how topical tacrolimus regulates cutaneous inflammatory conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06779.x
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  • 10
    Electronic Resource
    Electronic Resource
    Psoriatic patients with arthropathy show significant expression of free HLA class I heavy chains on circulating monocytes: a potential role in the pathogenesis of psoriatic arthropathy (2004)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 151 (2004), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Surface free heavy chains on monocytes were recently implicated in playing a role in the pathogenesis of several forms of arthritis.Objectives  To determine the expression of surface free heavy chains (recognized by monoclonal antibody HC10) on peripheral blood mononuclear cells of psoriatic patients with or without arthropathy.Methods  Twenty-eight psoriatic patients from the dermatology outpatient clinic were included in this study. Blood samples were collected during outpatient visits and clinical characteristics of the patients were documented. Quantitative analyses of circulating mononuclear cells were performed using flow cytometry.Results  Circulating monocytes showed higher expression of HC10 compared with circulating lymphocytes (P 〈 0·05). Psoriatic patients with arthropathy showed elevated expression of HC10 on peripheral blood monocytes compared with those without arthropathy (P 〈 0·05). Among the arthropathic group, those without the human leucocyte antigen (HLA)-B27 allele showed even higher expression of HC10 on circulating monocytes compared with those possessing HLA-B27 (P 〈 0·05). The polyarthropathic subgroup showed the highest HC10 expression, but the level of expression was not high enough to be of statistical significance compared with other arthropathic subgroups. No correlation was found between psoriatic skin involvement and the expression of HC10 on circulating monocytes.Conclusions  The presence of free heavy chains on circulating monocytes is closely associated with psoriatic arthropathy, while the expression of free heavy chains on circulating monocytes has no significant influence on psoriatic skin lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.05890.x
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