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-α 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-α 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-α receptor subunits by examining the mitogenic responses of cells to PDGF-AA, specific binding of 125I-labeled PDGF-AA, immunofluorescent analysis of PDGF-α receptor subunits, and PDGF-α 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-α receptor subunits, and in PDGF-α 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-α receptor subunits beyond that achieved with these factors individually. These experiments identify IL-1β, along with TGF-β, as significant inhibitors of PDGF stimulation in human PDL cells, acting through the down-regulation of PDGF-α receptor subunit expression.
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