involucrin and Lichen-Planus--Oral

Oral lichen planus (OLP) characterized by interface mucositis frequently shows hyper-keratinization. To clarify mechanisms of excess keratinization, we investigated key molecules for cornified cell envelope (CE).. Involucrin (IVL), loricrin (LOR), transglutaminase 1 (TGase 1) and transglutaminase 3 (TGase 3) were immunohistochemically examined in 20 specimens of OLP; five specimens of buccal mucosa served as controls. Subsequently, the data were statistically analyzed.. IVL in OLP was localized in the cell membrane, in contrast to its localization in the cytoplasm in controls. No positive reaction indicative of LOR was noted in any specimens. Although the TGase 1 localization in controls was restricted to the upper three-quarters of the membrane, the localization in OLP was in both membrane and in the cytoplasm of full thickness mucosal layers. The TGase 3 localization pattern was dramatically altered from cytoplasmic to membranous in OLP.. Our data suggest that aberrant TGase 1 and TGase 3 localization and distribution are closely related to hyper-keratinization in OLP. This is the first report of ectopic transglutaminase localization in OLP.

Topics: Cell Membrane; Epithelium; Humans; Intracellular Space; Keratins; Lichen Planus, Oral; Middle Aged; Protein Precursors; Transglutaminases

Bone morphogenic protein (BMP-4) is a member of transforming growth factor (TGF-beta) family and involved in various functions including apoptosis during neural ectoderm development. The objective of this study is to determine whether BMP-4 is involved in apoptosis, one characteristic, of human oral lichen planus (OLP).. Immunohistochemistry and in situ hybridization for BMP-4 were carried out in OLP (n = 21) and normal human oral mucosa (NOM, n = 31). Five tissue samples from NOM and OLP were underwent reverse transcriptase-polymerase chain reaction (RT-PCR). In vitro organ culture of oral mucosa was carried out with beads soaked with various concentration of BMP-4 (0.1, 1, and 10 microg/ml). The samples from in vitro organ culture were undergone haematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling technique (TUNEL) assay, and immunohistochemical study with p53, matrix metalloproteinases (MMP)-1, and MMP-3. Involucrin expression was determined by western blot analysis after treatment with BMP-4 or TGF-beta1 on human oral keratinocytes.. In immunohistochemical analysis, expression of BMP-4 was higher in OLP than NOM. BMP-4 mRNA expression was also detected in epithelial cells of both NOM and OLP together with underlying T-lymphocytes by in situ hybridization and RT-PCR. In oral mucosa organ culture, BMP-4 soaked beads induced apoptosis of epithelial cells. Acantolysis combined with apoptosis in oral epithelium was observed at 1 microg/ml of BMP-4 beads and it was due in part to the induction of p53 and MMP-1. Even MMP-3 induction was found in lower concentration of BMP-4 (0.1 and 1 microg/ml). Moreover, the expression of MMP-1 and MMP-3 was also observed in OLP. Recombinant BMP-4 or TGF-beta1 increased involucrin expression in human oral keratinocytes cell line.. Expression of BMP-4 of epithelial cells was higher in OLP than NOM. High concentration of BMP-4 caused an apoptosis of oral epithelial cells in oral mucosa organ culture. Therefore, over-expression of BMP-4 is one causing factor for apoptosis of oral epithelial cells through upregulation of p53, MMP1 and MMP3 in OLP.

Topics: Adult; Apoptosis; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins; Cells, Cultured; DNA Fragmentation; Epithelial Cells; Female; Humans; Keratinocytes; Lichen Planus, Oral; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 3; Middle Aged; Mouth Mucosa; Organ Culture Techniques; Protein Precursors; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Suppressor Protein p53; Up-Regulation