PDGF-ALPHA RECEPTOR SUBUNIT EXPRESSION DOWN-REGULATED BY IL-1-BETA INHUMAN PERIODONTAL-LIGAMENT CELLS

The responses of cells to the distinct PDGF isoforms have been correla ted directly to the relative numbers of specific PDGF receptor subunit s on the cell surface. The modulation of PDGF-alpha receptor subunits, the major subunit expressed in human periodontal ligament (PDL) cells , by cytokines present in the periodontal wound site, such as interleu kin-1 (IL-1), may be an important factor influencing regenerative outc omes. The purpose of the present study was to examine the effects of I L-1 beta on PDGF-alpha receptor subunit expression in human PDL cells. Primary cultures of human PDL cells were treated with IL-1 beta over a range of concentrations. We assessed PDGF-alpha receptor subunits by examining the mitogenic responses of cells to PDGF-AA, specific bindi ng of I-125-labeled PDGF-AA, immunofluorescent analysis of PDGF-alpha receptor subunits, and PDGF-alpha receptor subunit mRNA levels using N orthern blot analysis. The results demonstrate a significant concentra tion-dependent decrease in H-3-thymidine incorporation in response to PDGF-AA following IL-1 beta treatment (p < 0.001). This decreased resp onse correlated directly with IL-1-induced decreases in I-125-labeled PDGF-AA binding (p < 0.01), the numbers of immunolabeled PDGF-alpha re ceptor subunits, and in PDGF-alpha receptor subunit mRNA levels. Howev er, when combined with TGF-beta, IL-1 beta did not show additional dow n-regulation in proliferative response to PDGF-AA or PDGF-alpha recept or subunits beyond that achieved with these factors individually. Thes e experiments identify IL-1 beta, along with TGF-beta, as significant inhibitors of PDGF stimulation in human PDL cells, acting through the down-regulation of PDGF-alpha receptor subunit expression.