Calkins C C, Platt K, Potempa J, Travis J
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA.
J Biol Chem. 1998 Mar 20;273(12):6611-4. doi: 10.1074/jbc.273.12.6611.
Porphyromonas gingivalis is one of the major pathogens associated with adult periodontitis, a major chronic inflammatory disease. Potent proteinases elaborated by these bacteria aid directly and indirectly in both the development of the pathophysiology of the disease and in host defense evasion. For these reasons they are considered key virulence factors. To investigate whether possible immune evasion mechanisms involve the dysregulation of the host cytokine network, we examined the ability of P. gingivalis cysteine proteinases, including Arg-specific gingipains HRGP and RGP2 and Lys-specific KGP, to degrade the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). All three gingipains rapidly degraded TNF-alpha as exhibited by immunoblot analysis. Moreover, all biological activity was significantly reduced over extended incubation periods with the proteinases tested, whereas the host neutrophil proteinases were ineffective. These results indicate that the gingipain proteinases elaborated by P. gingivalis are capable of disrupting the cytokine network at the site of infection through the degradation of the proinflammatory cytokine TNF-alpha, suggesting the removal of one of several mediators important to the function of polymorphonuclear leukocytes. Such a mechanism is likely to be utilized by other infective organisms not only for survival but also for growth and proliferation.
牙龈卟啉单胞菌是与成人牙周炎（一种主要的慢性炎症性疾病）相关的主要病原体之一。这些细菌产生的强效蛋白酶直接或间接地有助于疾病病理生理学的发展以及逃避宿主防御。由于这些原因，它们被认为是关键的毒力因子。为了研究可能的免疫逃避机制是否涉及宿主细胞因子网络的失调，我们检测了牙龈卟啉单胞菌半胱氨酸蛋白酶（包括精氨酸特异性牙龈蛋白酶HRGP和RGP2以及赖氨酸特异性KGP）降解促炎细胞因子肿瘤坏死因子-α（TNF-α）的能力。免疫印迹分析显示，所有三种牙龈蛋白酶都能迅速降解TNF-α。此外，在所测试的蛋白酶长时间孵育后，所有生物活性均显著降低，而宿主中性粒细胞蛋白酶则无效。这些结果表明，牙龈卟啉单胞菌产生的牙龈蛋白酶能够通过降解促炎细胞因子TNF-α破坏感染部位的细胞因子网络，这表明去除了对多形核白细胞功能重要的几种介质之一。这种机制可能被其他感染性生物体利用，不仅用于生存，还用于生长和增殖。
