Search

Loricrin is a major component of the epidermal cornified cell envelope, and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific regulatory mechanisms for activation and suppression of loricrin gene transcription in differentiated keratinocytes. Here, we identified a regulatory element in the proximal promoter region of the loricrin gene involved in suppression of its expression in keratinocytes. A database search indicated that this sequence contained a POU transcription factor binding motif. Electrophoretic mobility shift assay revealed that Oct-1, Oct-6, and Oct-11 actually bind to the motif. Constructs with point mutations in the POU-binding motif showed increased reporter activity, indicating that the POU factors negatively regulate loricrin gene transcription. Cotransfection experiments suggested that Oct-6 and Oct-11 suppress loricrin gene transcription in a cooperative manner with AP-1 and Sp1. Furthermore, in vitro experiments indicated that the Oct-6 and Oct-11 can physically associate with both AP-1 factors and Sp1/Sp3. These findings indicate that Oct-6 and Oct-11 contribute to the regulation of loricrin gene transcription via interaction with AP-1 factors and Sp1/Sp3. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type I ( NF1) is associated with typical hypervascular tumors, including neurofibroma, glioma, malignant peripheral nerve sheath tumors ( MPNST) and glomus tumors. Previously, we and other groups reported that neurofibromas showed high-level expression of vascular endothelial growth factor ( VEGF), a potent angiogenic factor involved in neovascularization. However, the molecular mechanism underlying the upregulation of VEGF in neurofibromas remains unclear. In this study, we examined the effects of Nf1 gene silencing on VEGF expression in Schwann cell and non-Schwann cell line and the upstream mTOR- HIF-1α - VEGF pathway in Schwann cell line. The results indicated that Nf1 gene silencing by lentiviral-mediated RNA interference resulted in elevated expression of VEGF, HIF-1α and phosphorylated mTOR at the protein level. The results obtained from Nf1 gene silencing in murine Schwann cell line analogously suggest that NF1 gene haploinsufficiency in human tumor Schwann cells may directly elicit upregulation of VEGF expression without the tumor microenvironment by activation of the mTOR- HIF-1α - VEGF pathway. We also showed that interleukin-6 is upregulated in Nf1 gene knock-down Schwann cells at the protein level. [ABSTRACT FROM AUTHOR]

Abstract: We studied the expression of angiogenic factors (vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor and hepatocyte growth factor) in cutaneous neurofibroma samples from patients with neurofibromatosis-1. Immunohistochemical staining and the reverse transcribed polymerase chain reaction (RT-PCR) method demonstrated that vascular endothelial and basic fibroblast growths factor are highly expressed in neurofibroma cells at both the protein and mRNA level. These data suggest that vascular endothelial and basic fibroblast growth factors may contribute to both the angiogenesis and hypervascularity of neurofibromas. [ABSTRACT FROM AUTHOR]

In order to investigate the re-epithelialization process during wound healing, the hair on the back of guinea pigs was shaved and then excisional wounds were made through the entire thickness of the skin. Histological changes were observed and changes in the expression of different cytokeratin polypeptides were examined using an immunohistochemical technique. Immunohisto chemical study revealed that the proliferating and migrating keratinocytes expressed the same cytokeratins as the basal cells of normal epidermis. In addition, the entire epidermis of fairly remote areas from the edges of the wound where no thickening was observed showed a temporarily abnormal staining pattern. The suprabasal cells in the regenerating epidermis temporarily expressed cytokeratins not only specific for suprabasal cells but also specific for basal cells. The cytokeratins expressed in normal basal keratinocytes were also present in the thickened granular layers. These data indicate that the expression of cytokeratins in the epidermal keratinocytes (even in fairly remote areas from the wound edges) changes during wound healing, that the origin of the migrating keratinocytes from the remaining epidermis seems to be the basal cells in the epidermis, and that the appearance of keratohyalin granules is not related to changes in cytokeratin expression. [ABSTRACT FROM AUTHOR]

Despite various studies, there are serious disagreements about the cellular differentiation of papillary eccrine adenoma. in the present study, 2 specimens of papillary eccrine adenoma were analyzed by immunohistochernical techniques, using a panel of monoclonal antibodies against keratins, to elucidate its differentiation. Histopathologically, the tumor was composed of multiple tubular structures lined by two or more layers of epithelial cells. The luminal cells of the tubules were flattened or cuboidal. The former were noted in large dilated tubules. The latter were usually observed in small-to-moderate-sized tubules, and formed intraluminal papillary projections in some tubules. Immunohistochemically, there were two kinds of cuboidal cells in the luminal layers of the tubules. Most of the large dilated tubules and some of the small-to-moderate-sized tubules expressed immunophenotypes similar to those of the eccrine dermal duct. The other tubular structures, including the small tubules resembling those of syringoma, expressed immunophenotypes similar to those of the transitional portions between the dermal ducts and the secretory segments of eccrine glands. From the above comparative studies, papillary eccrine adenoma is considered to differentiate towards the dermal duct and the transitional portions between the dermal ducts and the secretory segments of eccrine glands. [ABSTRACT FROM AUTHOR]

Describes the identification of an immunoglobulin E (IgE)-binding protein derived from Staphylococcus aureus by screening a genomic DNA library with sera from patients with atopic dermatitis. Technique used in skin testing and immunotherapy protocols for patients with allergic conditions; Views on the Staphylococcus aureus infection; Manner in which serum IgE antibodies to Staphylococcus aureus have been demonstrated in atopic dermatitis patients.