Human Keratinocytes Express Cellular Prion-Related Proteinin Vitro and during Inflammatory Skin Diseases

Abstract

Prion diseases are transmissible spongiform encephalopathies of humans and animals characterized by the accumulation of a proteinase-resistant isoform of the cellular prion-related protein (PrPc) within the central nervous system. In the present report we demonstrate for the first time the presence of PrPc on squamous epithelia of normal and diseased human skin and show that inflammatory cytokines regulate PrPc expression in cultured human keratinocytes (KCs). By immunohistochemistry, only little expression of PrPc, which was mainly confined to KCs, was detected in normal skin. In contrast, in inflammatory skin diseases including psoriasis and contact dermatitis, PrPc was strongly present on both KCs and infiltrating mononuclear cells. Strong PrPc expression was also observed in squamous cell carcinomas and viral warts whereas basal cell carcinomas were mostly negative. In mucous membranes of the upper digestive tract and the genital region, distinct PrPc expression by basal squamous epithelial cells was a constant feature. In tissue culture, primary KCs constitutively expressed PrPc mRNA and protein. Exposure of these cells to transforming growth factor (TGF)-alpha or interferon (IFN)-gamma led to an increase of PrPc protein expression. The presence of PrPc on epithelial cells of skin and mucous membranes suggests that these cells represent possible first targets for peripheral infection with prions.

Epithelial and endothelial expression of the green fluorescent protein reporter gene under the control of bovine prion protein (PrP) gene regulatory sequences in transgenic mice

“…It has been reported in keratinocytes (38), and we observed PrP c on the endothelial cells of the intestinal villi (Fig. 4H).…”

“…However, the analysis of the PrP-gfp tg mouse lines shows that the cellular specificity of the reporter gene expression correlates quite well with the endogenous Prnp gene expression. For instance, the cerebellar Purkinje cells (16,20,21,34) in the brain (37), the keratinocytes in the skin (38), and the lymphocytes (23, 24) have been described previously as expressing PrP c and are gfp-fluorescent in the tg mice. This result indicates that the 6.9-kb segment of the 5Ј UTR region of the bovine PrP gene is sufficient to direct the expression of gfp in these cells.…”

Human FDC express PrPc invivo and invitro

“…1). After anti-PrP immunolabelling of cryosections with 3F4 antibody, the keratinocytes lining the crypts mainly at the level of basal cells were stained densely as it was previously reported by Pammer (Pammer et al, 1998), however, the germinal centres displayed a very low labelling. In the germinal centres, fine peroxidase reagent deposits were found along the intercellular spaces of the constituent cells (Fig.…”

The evidence of associations between prion protein genotype and production, reproduction, and health traits in sheep

“…Some suggested roles are reviewed [43] and include signal transduction, synaptic transmission, and protection against cell death. The prion protein is expressed in a wide variety of different organs, tissues and cells throughout the foetal and adult body and in cell lines [4,37,57,60,65,66,78].…”