THE ROLE OF INFLAMMATORY MEDIATORS IN THE PATHOGENESIS OF PERIODONTAL-DISEASE
THE ROLE OF INFLAMMATORY MEDIATORS IN THE PATHOGENESIS OF PERIODONTAL-DISEASE
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DOI：
10.1111/j.1600-0765.1991.tb01649.x
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发表时间：
1991-05-01
影响因子：
3.5
通讯作者：
PAGE, RC
中科院分区：
文献类型：
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作者：
PAGE, RC
细菌在牙周炎发生中的作用是有据可查的，最终结果是牙槽骨和牙周结缔组织的破坏，很容易观察到，但这两个时间点之间发生的事件仍然不清楚，是本文的重点。细菌通过激活宿主防御细胞间接诱导组织破坏，宿主防御细胞又产生和释放刺激结缔组织破坏效应物的介质。微生物菌斑的成分能够诱导包括淋巴细胞、巨噬细胞和中性粒细胞在内的炎症细胞的初始浸润。微生物组分，特别是脂多糖（LPS），具有激活巨噬细胞以合成和分泌多种分子的能力，所述分子包括细胞因子白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）、胡萝卜素，特别是PGE 2和水解酶。同样地，细菌物质激活T淋巴细胞，它们产生IL-1和光敏素（LT），一种具有与TNF-α非常相似的性质的分子。这些细胞因子表现出强有力的促炎和分解代谢活性，并在牙周组织破坏中发挥关键作用。它们诱导成纤维细胞和巨噬细胞产生中性金属蛋白酶，如前胶原酶和前基质溶解素、丝氨酸蛋白酶尿激酶型纤溶酶原激活物（u-PA）、金属蛋白酶组织抑制剂（TIMP）和胰高血糖素。u-PA将纤溶酶原转化为纤溶酶，纤溶酶可激活中性金属蛋白酶酶原，这些酶降解细胞外基质成分。TIMP使活性酶失活，从而阻断进一步的组织降解。在这个过程中涉及几种放大和抑制机制。虽然LPS激活巨噬细胞产生IL-1，但IL-1是自刺激性的，因此可以扩增并维持其自身的产生。干扰素-γ（INF-γ）抑制自身刺激，但它增强LPS诱导的IL-1产生。PGE 2通过抑制IL-1和TNF-α的产生来控制整个过程。此外，活化的细胞产生结合IL-1受体但不诱导IL-1结合的生物学后果的IL-1受体拮抗剂。其他细胞因子如转化生长因子-β（TGF-β）抑制金属蛋白酶和u-PA的产生。因此，组织降解的进展和程度可能主要由IL-1、TNF-α和相关细胞因子、竞争性分子如IL-1受体拮抗剂和抑制性分子如TGF-β和PGE 2的相对浓度和半衰期决定。这些分子控制潜伏和活性金属蛋白酶和u-PA的水平，TIMP的可用性和浓度决定了降解活性的程度和持续时间。
The role of bacteria in the initiation of periodontitis is well-documented and the end result, destruction of the alveolar bone and periodontal connective tissue, is readily observed; but the events occurring between these two points in time remain obscure and are the focus of this paper. Bacteria induce tissue destruction indirectly by activating host defense cells, which in turn produce and release mediators that stimulate the effectors of connective tissue breakdown. Components of microbial plaque have the capacity to induce the initial infiltrate of inflammatory cells including lymphocytes, macrophages, and PMNs. Microbial components, especially lipopolysaccharide (LPS), have the capacity to activate macrophages to synthesize and secrete a wide array of molecules including the cytokines interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-alpha), prostaglandins, especially PGE2, and hydrolytic enzymes. Likewise, bacterial substances activate T lymphocytes and they produce IL-1 and lymphotoxin (LT), a molecule having properties very similar to TNF-alpha. These cytokines manifest potent proinflammatory and catabolic activities, and play key roles in periodontal tissue breakdown. They induce fibroblasts and macrophages to produce neutral metalloproteinases such as procollagenase and prostromelysin, the serine proteinase urokinase-type plasminogen activator (u-PA), tissue inhibitor of metalloproteinase (TIMP), and prostaglandins. u-PA converts plasminogen into plasmin, which can activate neutral metalloproteinase proenzymes, and these enzymes degrade the extracellular matrix components. TIMP inactivates the active enzymes and thereby blocks further tissue degradation. Several amplification and suppression mechanisms are involved in the process. While LPS activates macrophages to produce IL-1, IL-1 is autostimulatory and can therefore amplify and perpetuate its own production. Interferon-gamma (INF-gamma) suppresses autostimulation, but it enhances LPS-induced IL-1 production. PGE2 exerts a control over the whole process by suppressing production of both IL-1 and TNF-alpha. Furthermore, the activated cells produce an IL-1 receptor antagonist that binds to the IL-1 receptor but does not induce the biologic consequences of IL-1 binding. Other cytokines such as transforming growth factor-beta (TGF-beta) suppress production of metalloproteinases and u-PA. Thus the progression and extent of tissue degradation is likely to be determined in major part by relative concentrations and half-life of IL-1, TNF-alpha, and related cytokines, competing molecules such as the IL-1 receptor antagonist, and suppressive molecules such as TGF-beta and PGE2. These molecules control levels of latent and active metalloproteinase and u-PA, and the availability and concentration of TIMP determines the extent and duration of degradative activity.