Interferon-γ Regulates Human Follicular Dendritic Cell-Secreted Protein Gene Expression in Gingival Epithelial Cells

Follicular dendritic cell-secreted protein (FDC-SP) is a low-molecular-weight secreted protein produced by follicular dendritic cells, the periodontal ligament and the junctional epithelium (JE). To analyze the transcriptional regulation of FDC-SP by interferon-γ (IFN-γ), real-time PCR, Western blot, luciferase (LUC) and gel mobility shift assays were performed using Ca9-22 human gingival epithelial cells. IFN-γ (10 ng/ml) increased FDC-SP mRNA levels at 3 to 24 h and protein levels at 12 h. IFN-γ increased the activities of LUC constructs containing the FDC-SP gene promoter sequence -345 bp and -717 bp upstream from the transcription start site. IFN-γ-induced LUC activities of -345FDC-SP and -717FDC-SP were inhibited by fludarabine, a signal transducer and activator of transcription 1 (STAT1) inhibitor. Gel shift assays showed that IFN-γ increased phosphorylated STAT1 (p-STAT1) binding to gamma interferon activation site 2-3 (GAS2-3) and GAS4 elements at 12 h. These results suggest that IFN-γ increases FDC-SP gene expression through the binding of phosphorylated STAT1 to the GAS2-3 and GAS4 elements in the human FDC-SP gene promoter sequence.