PDGF-α Receptor Subunit Expression Down-regulated by IL-1β in Human Periodontal Ligament Cells

The responses of cells to the distinct PDGF isoforms have been correlated directly to the relative numbers of specific PDGF receptor subunits on the cell surface. The modulation of PDGF-a receptor subunits, the major subunit expressed in human periodontal ligament (PDL) cells, by cytokines present in the periodontal wound site, such as interleukin-1 (IL-1), may be an important factor influencing regenerative outcomes. The purpose of the present study was to examine the effects of IL-1β on PDGF-a receptor subunit expression in human PDL cells. Primary cultures of human PDL cells were treated with IL-1β over a range of concentrations. We assessed PDGF-a receptor subunits by examining the mitogenic responses of cells to PDGF-AA, specific binding of 125I-labeled PDGF-AA, immunofluorescent analysis of PDGF-a receptor subunits, and PDGF-a receptor subunit mRNA levels using Northern blot analysis. The results demonstrate a significant concentration-dependent decrease in 3H-thymidine incorporation in response to PDGF-AA following IL-1β treatment (p < 0.001). This decreased response correlated directly with IL-1-induced decreases in 125I-labeled PDGF-AA binding (p < 0.01), the numbers of immunolabeled PDGF-a receptor subunits, and in PDGF-a receptor subunit mRNA levels. However, when combined with TGF-β, IL-1β did not show additional down-regulation in proliferative response to PDGF-AA or PDGF-a receptor subunits beyond that achieved with these factors individually. These experiments identify IL-1 (3, along with TGF-β, as significant inhibitors of PDGF stimulation in human PDL cells, acting through the down-regulation of PDGF-a receptor subunit expression.