| Autor: |
Nares, Salvador, Ng, May C., Dill, Russell E., Park, Bina, Cutler, Christopher W., Iacopino, Anthony M. |
| Zdroj: |
Journal of Periodontology; March 1996, Vol. 67 Issue: 3 p271-278, 8p |
| Abstrakt: |
Cyclosportne a (csa) is a widely usedimmunosuppressant 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 PDGFB 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. J Periodontol 1996;67:271–278. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Plný text