Transcriptional regulation of human follicular dendritic cell-secreted protein gene by interleukin-6.

Abstract

Follicular dendritic cell-secreted protein (FDC-SP) is produced by follicular dendritic cells, periodontal ligament and junctional epithelium (JE). JE exists immediately apical to the bottom of the pocket and binds enamel with hemidesmosomes to protect the periodontium from bacterial infection. To analyze the transcriptional regulation of the FDC-SP gene by interleukin-6 (IL-6), we performed real-time PCR, Western blotting, immunofluorescence, luciferase (LUC) assays, gel mobility shift and chromatin immunoprecipitation (ChIP) assays using Ca9-22 and Sa3 gingival epithelial cells. IL-6 increased FDC-SP mRNA and protein levels at 3-24 h. IL-6 increased LUC activities of the LUC constructs containing FDC-SP gene promoter sequences from -116 to -717 bp upstream from the transcriptional start site. IL-6 induced LUC activities of -345FDCSP were inhibited by protein kinase A, tyrosine kinase, mitogen-activated protein kinase kinase, phosphoinositide 3-kinase, signal transducer, activator of transcription 3 (STAT3) and glycoprotein 130 inhibitors. Gel shift and ChIP assays showed that IL-6 induced Yin Yang1 (YY1), GATA binding protein (GATA), CCAAT/enhancer-binding protein (C/EBP) β, phosphorylated STAT3 (p-STAT3) binding to YY1, GATA, C/EBP2, C/EBP3 and GAS2-3 elements. These results indicate that IL-6 induces FDC-SP gene transcription YY1, GATA, C/EBP2, GAS2-3 and C/EBP3 elements in the human FDC-SP gene promoter, and suggesting that FDC-SP may be involved in the defense against JE in periodontium during the progression of periodontitis.