Inhibitory effect of TGF-β on expression of 230kD bullous pemphigoid antigen

Abstract

230-kD bullous pemphigoid antigen (BPAG1) is known as an autoantigen in bullous pemphigoid and is expressed exclusively in proliferating basal keratinocytes. TGFfJ is a growth factor that has pleiotropic effects on a wide range of target cells and induces differentiation of basal keratinocytes. Therefore. TGFfJ is postulated to inhibit BPAG1 expression. However. previous report conversely demonstrated an increase of BPAG1 expression by TGFfJ. In this study. to understand regulatory role of TGFfJ on BPAG1 functions. we examined the effect of TGFfJ on BPAG1 gene expression using cultured keratinocytes. This study showed that BPAG1 mRNA expression was inhibited by TGFfJ 1 in concentration higher than 1.0 ng/ml. Furthermore. incubation of the cells with TGFfJ 1 in the presence of cycloheximide demonstrated that newly synthesized protein was required for BPAG1 regulation. To understand the detailed mechanisms of BPAGI modulation by TGFfJ, we preformed transient transfection assay with a BPAGI promoter-CAT construct to know the detailed mechanisms of BPAG1 modulation by TGFfJ. The results revealed that calcium and IFNy inhibited BPAG1 expression at transcriptional level, but TGFfJ 1 is not responsible for that transcriptional inhibition, suggesting that TGFfJ may have differential molecular mechanism for down-regulation of BPAG 1 gene expression from the events induced by IFNy. Hirosaki Med. ]. 59: 7-14. 2007