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71.
Ultraviolet B induces hyperproliferation and modification of epidermal differentiation in normal human skin grafted on to nude mice 总被引:3,自引:0,他引:3
Del Bino S Vioux C Rossio-Pasquier P Jomard A Demarchez M Asselineau D Bernerd F 《The British journal of dermatology》2004,150(4):658-667
BACKGROUND: For ethical and technical reasons, the in vivo biological effects of ultraviolet (UV) radiation on skin are difficult to study in human volunteers. The use of human skin grafted on to nude mice may circumvent this difficulty. OBJECTIVES: To investigate the effects of a single moderate UVB exposure on human skin grafted on to nude mice. METHODS: Modifications of epidermal differentiation markers and patterns of keratin expression were assessed from 24 h to 14 days after a physiological UVB irradiation characterized by the induction of sunburn cells. RESULTS: During the first 48 h postexposure, involucrin, loricrin, transglutaminase type I, filaggrin and keratin K2e expression were altered together with the formation of abnormal horny layers. Constitutive keratin K14 was increased while keratin K10 expression was delayed. Newly synthesized keratins K6, K16, K17 and K19 were induced in parallel with an increase in the epidermal proliferation rate. A progressive normalization of both keratinocyte proliferation and differentiation took place during the following days, reaching completion within 2 weeks. CONCLUSIONS: Exposure of human skin to a UVB dose corresponding to a mild sunburn reaction induces epidermal hyperproliferation and alterations of several constitutive differentiation markers, as well as a drastic modification in the pattern of epidermal keratins. Although these modifications were shown to be progressively reversed in a single exposure model, the data also suggest that subsequent UV exposures occurring during the recovery period may lead to potentially deleterious long-term consequences, such as photoageing and photocarcinogenesis. Grafted human skin appeared to be an attractive and promising model for investigating the biological consequences of UVB radiation in vivo. 相似文献
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Biologic therapy of inflammatory bowel disease 总被引:26,自引:0,他引:26
Advancing knowledge regarding the biology of chronic inflammation has led to the development of specific biologic therapies that mechanistically target individual inflammatory pathways. Many biologic therapies are being evaluated for the treatment of the chronic inflammatory bowel diseases, Crohn's disease and ulcerative colitis. Biologic compounds proven to be effective for Crohn's disease include monoclonal antibodies to tumor necrosis factor (infliximab and CDP571) and to the leukocyte adhesion molecule alpha4 integrin (natalizumab). Other biologic compounds for which there is insufficient evidence to judge efficacy for inflammatory bowel disease include: p55 tumor necrosis factor binding protein (onercept); interferon alpha; interferon beta-1a; anti-interferon gamma antibody; anti-interleukin 12 antibody; p65 anti-sense oligonucleotide (blocks NF-kappaB); granulocyte colony stimulating factor, and granulocyte macrophage colony stimulating factor; anti-interleukin 2 receptor antibody; epidermal growth factor; keratinocyte growth factor 2 (repifermin); human growth hormone; anti-CD4 antibody; and anti-alpha4beta7 antibody. Biologic therapies that have been proven ineffective for inflammatory bowel disease include: interleukin 10; interleukin 11; anti-sense intercellular adhesion molecule-1; and the tumor necrosis factor receptor fusion protein etanercept. Based on the early successes of infliximab, CDP571 and natalizumab, it seems certain that biologic therapy will play an important role in the future treatment of inflammatory bowel disease. 相似文献
74.
de Nooij-van Dalen AG van Dongen GA Smeets SJ Nieuwenhuis EJ Stigter-van Walsum M Snow GB Brakenhoff RH 《International journal of cancer. Journal international du cancer》2003,103(6):768-774
The E48 antigen is a successfully explored molecular marker for the diagnosis and therapy of HNSCC. The applicability of E48 as an HNSCC-associated antigen, however, is restricted due to its heterogeneous expression in 30% of tumors; and identification of additional target antigens is therefore desired. E48 belongs to the Ly-6 antigen family, comprising a group of highly homologous, low m.w., GPI-anchored surface proteins, of which some show tissue-restricted expression patterns. To identify novel human HNSCC-associated Ly-6 members with squamous cell-associated expression patterns, we performed comprehensive gene-screening consisting of BLAST searches within GenBank databases, followed by expression analysis. Using this approach, the Ly-6K gene could be annotated as a novel member of the human Ly-6 family. Expression of the human Ly-6 genes E48, Ly-6K, PSCA, GML, RIG-E, G6C and Ly-6H was prescreened by qualitative RT-PCR and subsequently analyzed by quantitative RT-PCR in normal keratinocytes, HNSCC cell lines, normal mucosa, HNSCC tumors as well as normal peripheral blood and bone marrow cells. PSCA was highly expressed in normal mucosa, but 100-fold decreased expression was seen in HNSCC. For Ly-6H, GML and G6C, no or very low expression was observed in keratinocytes and HNSCC. Expression of RIG-E was high in normal and malignant squamous cells and in peripheral blood and bone marrow cells, thus limiting its applicability as an HNSCC-associated marker. In contrast, besides the E48 gene, the Ly-6K gene also appeared to be selectively expressed in HNSCC and normal squamous cells. Moreover, expression of Ly-6K was shown in HNSCC cell lines, in which no E48 expression could be detected. These data justify further evaluation of Ly-6K as potential target antigen for the diagnosis and therapy of HNSCC. 相似文献
75.
Cell attachment, as a biological process, is an important aspect with respect to graft survival and "take". With the ever-increasing use of cultured epithelial autografts for coverage and re-epithelialization of wounds, the assessment of keratinocyte adhesion in vitro has become a more common requirement in studies involving extracellular matrix proteins and their receptor molecules. Cell adhesion has been well-documented in immunological research, however keratinocyte adhesion has been investigated by manual counting (using methylene blue) or other less sensitive colorimetric methods. With the increase in number of fluorogenic probes available, their use as a sensitive alternative to radioactive labelling has been promoted in the literature. This study was carried out to investigate the possibility of using fluorescent probe 5,6-carboxyfluorescein diacetate succidimyl ester to achieve a more standardized assay in the assessment of keratinocyte adhesion. Adhesion was assessed on extracellular matrix proteins such as fibronectin, collagen types I & IV and laminin. We concluded that the fluorescent probe might provide greater sensitivity in measuring adhesion, however it may be cytotoxic to keratinocytes. Pre-labelling of keratinocytes may affect cellular functions such as adhesion and even proliferation and consequently the probe must be chosen with care. 相似文献
76.
Distribution and potential biologic function of the thrombin receptor PAR-1 on human keratinocytes 总被引:3,自引:0,他引:3
Algermissen B Sitzmann J Nürnberg W Laubscher JC Henz BM Bauer F 《Archives of dermatological research》2000,292(10):488-495
Thrombin has recently been shown not only to exert procoagulant activities, but also to induce mitogenic responses of different cell types involved in wound healing via binding to and cleavage of the thrombin receptor. In order to further explore these aspects of thrombin function, human keratinocytes (HaCaT cell line) were examined for their potential mitogenic responsiveness to thrombin and for the dependency of this process on the expression of the high-affinity thrombin receptor. Quiescent keratinocytes were stimulated in the mitogenic assay with alpha-thrombin and the thrombin receptor activating peptides TRAP42-55 (SFLLRNPNDKYEPY) and TRAP42-46 (SFLLR). A strong induction of cell proliferation was noted with alpha-thrombin, TRAP42-55 and TRAP42-46, but not with the "scrambled" peptide (FSLLR). These findings confirm that keratinocytes express the thrombin receptor and that the sequence of the first two amino acids of the generated neo-N-terminus are important for the activation of the receptor. Using cDNA fragments of the 5' coding sequence of the receptor, Northern blot analysis confirmed that HaCaT keratinocytes express the thrombin receptor. Expression of the receptor was also detected on normal human keratinocytes by immunohistochemistry and in situ hybridization. These data demonstrate the expression and biologic function of the human thrombin receptor on human keratinocytes, suggesting that thrombin, among other mediators, plays an important part in the orchestration of epidermal growth and repair processes. 相似文献
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80.
Jie Li Paula M. Farthing Martin H. Thornhill 《Journal of oral pathology & medicine》2000,29(9):438-444
Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC subfamily of chemokines. It is chemoattractant for monocytes, activated memory T cells and dendritic cells. We studied MCP-1 mRNA and protein production in cultured human oral keratinocytes (OK) and skin keratinocytes (SK). MCP-1 production was undetectable in resting keratinocytes. However, stimulation with tumour necrosis factors (TNF-alpha) or interferon-gamma (IFN-gamma) induced MCP-1 mRNA and protein synthesis in both cell types. Together, TNF-alpha and IFN-gamma acted synergistically to increase MCP-1 production. In each case MCP-1 production was greater for SK than OK. The kinetics of IFN-gamma-induced MCP-1 production were similar for both cell types, peaking around 72 h. In contrast, TNF-alpha induced a more rapid increase in MCP-1 production by SK than OK, peak production occurring after 24 and 72 h, respectively. IL-1alpha and IL-4 did not induce MCP-1 production. However, in combination with IFN-gamma, they induced a small extra increase in MCP-1 production in SK but not OK. 相似文献