The Effects of Interferon -gamma on the Expression of Bullous Pemphigoid Antigen Genes in Cultured Keratinocytes

Ryoo, Young Wook; Shin, Moon Seok; Lee, Kyu Suk

Abstract

BACKGROUND: Interferon-gamma(IFN-gamma) has been shown to regulate epidermal keratinocyte growth and differentiation and can be isolated from subepidermal vesicles in bullous pemphigoid (BP) patients. In general, the IFN-gamma effects ate up-regulatory, and the corresponding transcriptional mechanisms have been elucidated in the case of several genes. One of the markers of the mitotic basal cell phenotype is the expression of BP antigens (BFAG), two hemidesmosomal proteins that were initially recognized as autoantigens in BP.
OBJECTIVE
Since down-regulation of BPA gene expression is one of the earliest events during epidermal differentiation and BPAG is served as the target of autoantibodies, in this study, we examined the effect of IFN-gammaon the expression of the gene encoding the BPAG1 and 2.
METHODS AND RESULTS
Northern analysis revealed a dose dependent suppression of BPAG expression by IFN-gamma in cultured human skin keratinocytes from 3 different donors, and incubation of the cells with IFN-gamma in the presence of cycloheximide demonstrated that this effect reqiured ongoing protein synthesis. Transient transfections of cultured keratinocytes with BPAG1 promoter-chloramphenicol acetyltransferase reporter gene plasmids indicated marked suppression of the promoter activity by IFN-gamma.
CONCLUSION
This data, which inactivation of transcription of a basal keratinocyte-specific gene(BPAGl) by IFN-gamma. pravides new insight into the mechanisms of IFN-gamma mediated keratinocyte gene regulation and epidermal differentitation in inflammatory and blistering skin disease.