Trombone A P F, Ferreira S B, Raimundo F M, de Moura K C R, Avila-Campos M J, Silva J S, Campanelli A P, De Franco M, Garlet G P
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, FMRP/USP, SP, Brazil.
J Periodontal Res. 2009 Aug;44(4):443-51. doi: 10.1111/j.1600-0765.2008.01133.x. Epub 2008 Oct 7.
Inflammatory immune reactions that occur in response to periodontopathogens are thought to protect the host against infection, but may trigger periodontal destruction. However, the molecular and genetic mechanisms underlying host susceptibility to periodontal infection and to periodontitis development have still not been established in detail.
In this study, we examined the mechanisms that modulate the outcome of Aggregatibacter (Actinobacillus) actinomycetemcomitans-induced periodontal disease in mice mouse strains selected for maximal (AIRmax) or minimal (AIRmin) inflammatory reactions.
Our results showed that AIRmax mice developed a more severe periodontitis than AIRmin mice in response to A. actinomycetemcomitans infection, and this periodontitis was characterized by increased alveolar bone loss and inflammatory cell migration to periodontal tissues. In addition, enzyme-linked immunosorbent assays demonstrated that the levels of the cytokines interleukin-1beta, tumor necrosis factor-alpha and interleukin-17 were higher in AIRmax mice, as were the levels of matrix metalloproteinase (MMP)-2, MMP-13 and receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA levels. However, the more intense inflammatory immune reaction raised by the AIRmax strain, in spite of the higher levels of antimicrobial mediators myeloperoxidase and inducible nitric oxide synthase, did not enhance the protective immunity to A. actinomycetemcomitans infection, because both AIRmax and AIRmin strains presented similar bacterial loads in periodontal tissues. In addition, the AIRmax strain presented a trend towards higher levels of serum C-reactive protein during the course of disease.
Our results demonstrate that the intensity of the inflammatory immune reaction is associated with the severity of experimental periodontitis, but not with the control of A. actinomycetemcomitans periodontal infection, suggesting that the occurrence of hyperinflammatory genotypes may not be an evolutionary advantage in the complex host-pathogen interaction observed in periodontal diseases.
针对牙周病原体发生的炎性免疫反应被认为可保护宿主免受感染，但也可能引发牙周组织破坏。然而，宿主对牙周感染及牙周炎发展易感性的分子和遗传机制仍未完全明确。
在本研究中，我们检测了在对牙龈卟啉单胞菌诱导的牙周疾病反应中，调节炎症反应最大（AIRmax）或最小（AIRmin）的小鼠品系中牙周疾病转归的机制。
我们的结果显示，在感染牙龈卟啉单胞菌后，AIRmax小鼠比AIRmin小鼠发生更严重的牙周炎，其特征为牙槽骨吸收增加以及炎性细胞向牙周组织迁移。此外，酶联免疫吸附测定表明，AIRmax小鼠中细胞因子白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-17的水平更高，基质金属蛋白酶（MMP）-2、MMP-13和核因子-κB受体活化因子配体（RANKL）的mRNA水平也更高。然而，尽管AIRmax品系引发了更强烈的炎性免疫反应，且具有更高水平的抗菌介质髓过氧化物酶和诱导型一氧化氮合酶，但并未增强对牙龈卟啉单胞菌感染的保护性免疫，因为AIRmax和AIRmin品系在牙周组织中的细菌载量相似。此外，在疾病过程中，AIRmax品系的血清C反应蛋白水平有升高趋势。
我们的结果表明，炎性免疫反应的强度与实验性牙周炎的严重程度相关，但与牙龈卟啉单胞菌牙周感染的控制无关，这表明在牙周疾病中观察到的高炎症基因型的出现可能并非复杂宿主-病原体相互作用中的进化优势。
