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Lesional Keratinocytes (lesional + keratinocyte)
Selected AbstractsCCL28 production in HaCaT cells was mediated by different signal pathways from CCL27EXPERIMENTAL DERMATOLOGY, Issue 2 2006Shinji Kagami Abstract:, Both CCL27 and CCL28 are ligands for CCR10 and attract CCR10+ lymphocytes. We previously demonstrated that CCL27 and CCL28 were strongly expressed in sera and lesional keratinocytes of patients with atopic dermatitis and psoriasis vulgaris. However, the regulation of CCL27 and CCL28 production in keratinocytes has not been well documented. In this study, we showed that CCL27 and CCL28 expression and production by a human keratinocyte cell line, HaCaT cells, were strongly induced by inflammatory cytokines tumor necrosis factor-, and interleukin-1,. CCL27 production was downregulated by inhibitors of p38 mitogen-activated protein kinase and nuclear factor-kappa B (NF-,B). By contrast, CCL28 production was downregulated by inhibitors of extracellular signal-regulated kinase and NF-,B. Our study results suggest that CCL28 produced by keratinocytes is mediated by different signal pathways from CCL27 and that both CCL27 and CCL28 are involved in the pathogenesis of inflammatory skin diseases. [source] MMP-2, TIMP-2 and MT1-MMP are differentially expressed in lesional skin of melanocytic nevi and their expression is modulated by UVB-lightJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2002S. Krengel Background:, In malignant melanoma, recent studies have demonstrated an important role of matrix-metalloproteinase 2 (MMP-2), its co-activating enzyme membrane-type matrix-metalloproteinase 1 (MT1-MMP), and the endogenous inhibitor of MMP-2, tissue-inhibitor of matrix metalloproteinase 2 (TIMP-2). Melanocytic nevi are benign neoplasms of the melanocytic lineage, but may exhibit dysplastic features that can be difficult to distinguish from early stage melanoma. As shown in earlier studies, nevi show important morphological and phenotypical changes in response to ultraviolet light (UVB) irradiation. Objective:, To clarify the role of MMP-2, TIMP-2 and MT1-MMP in UVB-irradiated vs. non-irradiated melanocytic nevi. Methods:, Immunohistochemical comparison of the MMP-2, TIMP-2 and MT1-MMP expression pattern. Results:, MMP-2 is expressed by lesional keratinocytes and its expression is up-regulated by UVB-irradiation. MMP-2 expression was not observed in melanocytic cells. TIMP-2, by contrast, is predominantly expressed by melanocytic nevus cells, and its expression is in part down-regulated by UVB-irradiation. MT1-MMP is expressed by basal keratinocytes and to a weaker extent by melanocytic nevus cells. Conclusions:, MMP-2 expression by keratinocytes in nevi probably represents the result of activation of keratinocyte turnover in lesional epidermis. MMP-2 could play a role in the downward movement of junctional nevus cells into the dermis. The reduction of TIMP-2 expression in melanocytic cells by UV-light together with the enhanced expression of MMP-2 in the adjacent epidermis may promote basement membrane degradation. The expression pattern of MT1-MMP in close proximity to epithelial,mesenchymal interfaces underlines the synergistic role of MT1-MMP in this process. [source] Creation of psoriatic plaques: the ultimate tumor suppressor pathway.JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2001A new model for an ancient T-cell-mediated skin disease. From an oncological and immunological perspective, the T-cell-mediated induction of psoriatic plaques should be prone to malignant transformation as the phenotype of psoriatic plaques includes: chronic inflammation, epidermal hyperplasia, prolonged survival and elevated telomerase levels in lesional keratinocytes, as well as angiogenesis, exposure to carcinogens and immunosuppressants. However, conversion of a psoriatic plaque to squamous cell carcinoma is exceedingly rare. This paper explores the possible molecular mechanism for the tumor suppressor pathway in psoriatic lesions, with an emphasis on a putative senescence-switch involving p16. [source] Psoriatic skin expresses the transcription factor Gli1: possible contribution of decreased neurofibromin expressionBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2006H. Endo Summary Background, Psoriasis is a chronic inflammatory disorder of skin characterized by hyperproliferation of keratinocytes. Intracellular signalling pathways inducing the hyperproliferation of keratinocytes remain to be elucidated. An inhibitor of Hedgehog (Hh) signalling, cyclopamine, was recently reported to clear psoriatic skin lesions, suggesting involvement of the Hh signalling pathway in the hyperproliferation of lesional keratinocytes. We have previously observed activation of the Hh signalling pathway in Schwann cells of plexiform neurofibroma in neurofibromatosis type 1 (NF1), which results from functional loss of the NF1 encoding protein, neurofibromin. In psoriasis, deficiency of neurofibromin expression has been observed in lesional keratinocytes. Objectives, To investigate whether the Hh signalling pathway would be activated in psoriasis and whether inhibition of neurofibromin expression would enhance the activation of the Hh signalling pathway. Methods, Activation of the Hh signalling pathway was examined by protein expression of one of the target genes, GLI1, coding for the transcription factor Gli1. Immunohistochemical studies were performed on seven psoriatic skin samples and seven control normal skin samples with a standard immunoperoxidase technique. mRNA expression of GLI1 was analysed by reverse transcriptase,polymerase chain reaction in HaCaT cells transfected with double-strand small interfering RNA for NF1. Results, Our results showed Gli1 expression in psoriatic skin but not in control normal skin. Inhibition of neurofibromin expression in HaCaT cells upregulated mRNA expression of GLI1. Conclusions, Our findings indicate that the Hh signalling pathway is activated in psoriasis and that neurofibromin deficiency may upregulate the pathway. [source] | ||||||||||