title: PDGF-alpha receptor subunit expression down-regulated by IL-1beta in human periodontal ligament cells.
abstract: 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-alpha 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-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 binding of 125I-labeled PDGF-AA, immunofluorescent analysis of PDGF-alpha receptor subunits, and PDGF-alpha 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-1 beta 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-alpha receptor subunits, and in PDGF-alpha receptor subunit mRNA levels. However, when combined with TGF-beta, IL-1 beta did not show additional down-regulation in proliferative response to PDGF-AA or PDGF-alpha receptor subunits beyond that achieved with these factors individually. These 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.
authors.affiliation: Department of Periodontics, University of Texas Health Science Center, San Antonio 78284, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Oates
authors.forename: J F
authors.initials: JF
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Clinton
authors.forename: A M
authors.initials: AM
authors.lastname: Hoang
authors.forename: D T
authors.initials: DT
authors.lastname: Graves
authors.forename: D L
authors.initials: DL
authors.lastname: Cochran
mesh_terms: D000704:Analysis of Variance; D015152:Blotting, Northern; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D011869:Radioligand Assay; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor