Ingman T, Sorsa T, Suomalainen K, Halinen S, Lindy O, Lauhio A, Saari H, Konttinen Y T, Golub L M
Department of Periodontology, University of Helsinki, Finland.
J Periodontol. 1993 Feb;64(2):82-8. doi: 10.1902/jop.1993.64.2.82.
Tetracyclines have recently been shown to inhibit the activity of some but not all mammalian matrix metalloproteinases believed to mediate periodontal destruction. However, the specificity of this effect, which could have significant therapeutic implications for different periodontal diseases, has not been examined in detail. Doxycycline and 4-de-dimethylaminotetracycline (CMT-1) have been tested in vitro for their ability to inhibit human neutrophil and fibroblast interstitial collagenases and collagenase in human gingival crevicular fluid (GCF). The GCF samples were obtained from systemically healthy and insulin-dependent diabetic adult periodontitis patients and from localized juvenile periodontitis (LJP) patients. The concentrations of these 2 tetracyclines required to inhibit 50% of the collagenase activity (IC50) were found to be 15 to 30 microM for human neutrophil collagenase and for collagenase in GCF of systemically healthy and diabetic adult periodontitis patients. These concentrations approximate the tetracycline levels observed in vivo during treatment with these drugs. In contrast, human fibroblast collagenase and GCF collagenase from LJP patients were both relatively resistant to tetracycline inhibition; the IC50 for doxycycline and CMT-1 for these 2 sources of collagenase were 280 and 500 microM, respectively. Based on these and other findings, we propose the following: 1) that systemic levels of tetracycline may inhibit connective tissue breakdown by inhibiting neutrophil collagenase; 2) that tetracyclines do not inhibit fibroblast-type collagenase, which may help explain their lack of effect on normal connective tissue remodeling; 3) that tetracycline inhibition of collagenases may serve to identify the cellular origin of the enzyme; and 4) that tetracyclines can also prevent the oxidative activation of latent human procollagenases.(ABSTRACT TRUNCATED AT 250 WORDS)
最近研究表明，四环素可抑制部分而非全部据信介导牙周组织破坏的哺乳动物基质金属蛋白酶的活性。然而，这种效应的特异性对不同牙周疾病可能具有重要治疗意义，尚未得到详细研究。强力霉素和4-去二甲基氨基四环素（CMT-1）已在体外测试其抑制人中性粒细胞和成纤维细胞间质胶原酶以及人龈沟液（GCF）中胶原酶的能力。GCF样本取自全身健康和胰岛素依赖型糖尿病成年牙周炎患者以及局限性青少年牙周炎（LJP）患者。发现抑制50%胶原酶活性所需的这两种四环素浓度（IC50），对于人中性粒细胞胶原酶以及全身健康和糖尿病成年牙周炎患者GCF中的胶原酶而言，为15至30微摩尔。这些浓度接近这些药物治疗期间体内观察到的四环素水平。相比之下，LJP患者的人成纤维细胞胶原酶和GCF胶原酶对四环素抑制均相对耐药；强力霉素和CMT-1对这两种胶原酶来源的IC50分别为280和500微摩尔。基于这些及其他发现，我们提出以下观点：1）四环素的全身水平可能通过抑制中性粒细胞胶原酶来抑制结缔组织破坏；2）四环素不抑制成纤维细胞型胶原酶，这可能有助于解释它们对正常结缔组织重塑缺乏作用；3）四环素对胶原酶的抑制作用可能有助于确定该酶的细胞来源；4）四环素还可防止人潜在前胶原酶的氧化激活。（摘要截短于250词）
