230-kD類天疱瘡抗原発現に対するTGF-βの抑制効果

概要

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230-kD bullous pemphigoid antigen (BPAG1) is known as an autoantigen in bullous pemphigoid and isexpressed exclusively in proliferating basal keratinocytes. TGF-β is a growth factor that has pleiotropic effects ona wide range of target cells and induces differentiation of basal keratinocytes. Therefore. TGF-β is postulated toinhibit BPAG1 expression. However. previous report conversely demonstrated an increase of BPAG1 expressionby TGF-β. In this study. to understand regulatory role of TGF-β on BPAG1 functions. we examined the effectof TGF-β on BPAG1 gene expression using cultured keratinocytes. This study showed that BPAG1 mRNAexpression was inhibited by TGF-β1 in concentration higher than 1.0 ng/ml. Furthermore. incubation of thecells with TGF-β1 in the presence of cycloheximide demonstrated that newly synthesized protein was requiredfor BPAG1 regulation. To understand the detailed mechanisms of BPAGI modulation by TGF-β, we preformedtransient transfection assay with a BPAGI promoter-CAT construct to know the detailed mechanisms of BPAG1modulation by TGF-β. The results revealed that calcium and IFN-γ inhibited BPAG1 expression at transcriptionallevel, but TGF-β1 is not responsible for that transcriptional inhibition, suggesting that TGF-β may have differentialmolecular mechanism for down-regulation of BPAG1 gene expression from the events induced by IFN-γ.
弘前大学の論文