1999 Fiscal Year Final Research Report Summary
Cytological and pharmacological studies on the pathogenesis of nifedipine-associated gingival hyperplasia
| Project/Area Number |
09671945
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Conservative dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NOGUCHI Kazuyuki Tokyo Medical & Dental Univ. Dep. Dentistry, Research associate, 歯学部, 助手 (90218298)
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| Co-Investigator(Kenkyū-buntansha) |
CHIBA Kan Chiba University Dep. Pharmacology Professor, 薬学部, 教授 (40159033)
KITADA Kouichi Chiba University Dep. Medicine Professor, 医学部, 教授 (90110345)
YANAGISHITA Masaki Tokyo Medical & Dental Univ. Dep. Dentistry, Professor, 歯学部, 教授 (70132793)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Nifedipine / Gingival hyperplasia / Proteoglycan / Gingival fibroblast / Lipopolysaccharide / Cytokine |
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| Research Abstract |
1. We selected 12 periodontitis patients with gingival hyperplasia in response to nifedipine (responder group) and 4 periodontitis patients with no gingival hyperplasia in response to nifedipine who visited Dental hospital at Tokyo Medical and Dental University. The concentration of nifedipine in serum 6 h after intake of nifedipine was examined using high performance liquid chromatography. The concentration of nifedipine in serum tended to be associated with gingival hyperplasia index, but the association was not significant.
2. Human gingival fibroblasts (HGF) were obtained from responder group and periodontally healthy subjects. We examined the effect of nifedipine and its metabolite on proteoglycan production in HGF from responder group and in HGF from periodontally healthy subjects. Nifedipine induced proteoglycan production in a dose-dependent fashion in HGF from responder group. In contrast, nifedipine depressed proteoglycan production in a dose-dependent manner in HGF from periodontally healthy subjects. A metabolite of nifedipine had similar effects.
3. The effect of lipopolysaccharides (LPS) derived from P. gingivalis and A. actinomycetemcomitans on proteoglycan production was examined in HGF derived from periodontally healthy gingiva. The LPS had no effect on proteoglycan production.
4. The effect of various cytokines including IL-4, IL-13, INF-gamma and TNFalpha on protoglycan production was examined in HGF derived from periodontally healthy gingiva. IL-4 and IL-13 significantly enhanced total amounts of proteoglycans, but INF-gamma decreased them. TNFalpha increased proteoglycan production in the culture medium, but decreased it in the cytosol. Combination of IL-4 and TNFalpha or IL-13 and TNFalpha synergistically upregulated proteoglycan production in the culture medium and slightly enhanced it in the cytosol.
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