Cyclosporine A upregulates platelet-derived growth factor B chain in hyperplastic human gingiva

Salvador Nares, May C. Ng, Russell E. Dill, Bina Park, Christopher W. Cutler, Anthony M. Iacopino

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Cyclosporine A (CSA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic components. A prominent side effect of CSA administration is gingival overgrowth (hyperplasia). It has been postulated that CSA alters fibroblast activity through effects on various growth factors/cytokines. However, as yet, data concerning the molecular mechanisms involved in pathologic connective tissue proliferation are preliminary in nature. Our previous investigations concerning phenytoin-induced effects on platelet-derived growth factor B (PDGF-B) gene expression have demonstrated that other drugs which cause gingival overgrowth can upregulate macrophage PDGF-B gene expression in vitro and in vivo. The purpose of the present study was to evaluate PDGF-B gene expression in gingival tissues of patients receiving CSA therapy and exhibiting gingival overgrowth to determine if similar PDGF-B upregulation occurs in response to CSA and to identify PDGF-B producing cells in these tissues. Quantitative competitive reverse transcription polymerase chain reaction (QC-RTPCR) techniques were utilized to measure PDGF-B mRNA levels in CSA overgrowth patients and normal controls (N = 6/group). Results were expressed as mean ± mRNA copy number and tested for significance using unpaired t-tests. Gingival samples were harvested (standardized for local inflammation at the sample site), total RNA was extracted, and QC-RTPCR was performed using specific PDGF-B primers and a corresponding competitive internal standard. CSA-treated patients exhibiting gingival overgrowth demonstrated approximately 48-fold increase in PDGF-B mRNA (7667.1 ± 477.4 copies for CSA patients vs. 158.2 ± 37.1 copies for controls; P < 0.001). Additionally, dual fluorescence immunohistochemistry for mature macrophage marker antigen (CD51) and intracellular PDGF-B was utilized to identify and localize PDGF-B producing cells in hyperplastic gingiva of CSA-treated patients. PDGF-B producing cells were demonstrated to be macrophages distributed in a non-uniform manner throughout the papillary connective tissue. These results further support the hypothesis that the molecular mechanisms responsible for drug-induced gingival overgrowth may involve upregulation of PDGF-B macrophage gene expression. We continue to investigate specific CSA-induced alterations of macrophage PDGF-B gene expression in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)271-278
Number of pages8
JournalJournal of periodontology
Volume67
Issue number3
DOIs
StatePublished - Mar 1996
Externally publishedYes

Keywords

  • cyclosporine A/adverse effects
  • gene expression
  • gingival hyperplasia/etiology
  • growth factor, platelet-derived
  • macrophages
  • wound healing

ASJC Scopus subject areas

  • Periodontics

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