Inactivation of tumor necrosis factor-α by proteinases (gingipains) from the periodontal pathogen, Porphyromonas gingivalis -: Implications of immune evasion
Inactivation of tumor necrosis factor-α by proteinases (gingipains) from the periodontal pathogen, Porphyromonas gingivalis -: Implications of immune evasion
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DOI：
10.1074/jbc.273.12.6611
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发表时间：
1998-03-20
影响因子：
4.8
通讯作者：
Travis, J
中科院分区：
文献类型：
--
作者：
Calkins, CC;Platt, K;Travis, J
牙龈卟啉单胞菌是引起成人牙周炎的主要病原菌之一。这些细菌产生的强有力的蛋白酶直接或间接地帮助疾病的病理生理学发展和宿主防御逃避。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，我们检查了牙龈卟啉单胞菌半胱氨酸蛋白酶（包括Arg特异性牙龈卟啉菌蛋白酶HRGP和RGP 2以及Lys特异性KGP）降解促炎细胞因子肿瘤坏死因子-α（TNF-α）的能力。所有三种牙龈卟啉菌蛋白酶快速降解TNF-α，如免疫印迹分析所示。此外，所有的生物活性显着降低，在延长的孵育期与测试的蛋白酶，而主机中性粒细胞蛋白酶是无效的。这些结果表明，牙龈卟啉单胞菌加工的牙龈菌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，表明去除了对多形核白细胞功能重要的几种介质之一。这种机制很可能被其他感染性生物体利用，不仅用于生存，而且用于生长和增殖。
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.