Rapid and efficient inactivation of IL-6 gingipains, lysine- and arginine-specific proteinases from Porphyromonas gingivalis
Rapid and efficient inactivation of IL-6 gingipains, lysine- and arginine-specific proteinases from Porphyromonas gingivalis
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DOI：
10.1006/bbrc.1999.1075
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发表时间：
1999-08-11
影响因子：
3.1
通讯作者：
Potempa, J
中科院分区：
文献类型：
--
作者：
Banbula, A;Bugno, M;Potempa, J
细胞因子网络的解除管制是病原菌调节和逃避宿主免疫应答的重要适应。在这里，我们描述了IL-6被来自牙龈卟啉单胞菌的精氨酸和赖氨酸特异性蛋白酶（称为RGP-A， RGP-B和KGP）快速有效地切割和失活。在IL-6多肽链n端区域的R18和Q19之间定位了rgp的主要切割位点之一；然而，KGP和rgp都在多肽链的c端区域切割IL-6。在这些最初的蛋白水解裂解后，IL-6被每一种酶进一步降解。虽然KGP是最有效的IL-6降解蛋白酶，但所有牙龈痛介导的IL-6的初始c端裂解已经足以使该细胞因子失活。我们的数据与观察结果一致，在牙周炎中，白细胞介素6浓度在细菌菌斑附近的牙龈组织中最低，而在感染区域周围检测到该细胞因子浓度显著升高。因此，牙痛引起的IL-6降解可能是影响牙周菌斑远端与近端促炎反应平衡的另一种机制，(C) 1999年学术出版社。
Deregulation of the cytokine network is an important adaptation of pathogenic bacteria to modulate and evade a host immune response. Here we describe that IL-6 is rapidly and efficiently cleaved and inactivated by the arginine- and lysine-specific proteinases from Porphyromonas gingivalis, referred to as RGP-A, RGP-B, and KGP. One of the primary cleavage sites for RGPs has been mapped between R18 and Q19 within the N-terminal region of the IL-6 polypeptide chain; however, both KGP and RGPs cleave IL-6 within the C-terminal region of the polypeptide chain. After these initial proteolytic cleavages, IL-6 is further degraded by each of the enzymes tested. Although KGP is the most potent IL-6-degrading proteinase, the initial C-terminal cleavage of IL-6 mediated by all gingipains is already sufficient to inactivate this cytokine. Our data are consistent with the observation that in periodontitis the IL-6 concentration is lowest in the gingival tissue adjacent to bacterial plaque, whereas significantly elevated concentrations of this cytokine are detected around the infected area. Degradation of IL-6 by gingipains may, therefore, represent an additional mechanism which influences the balance between pro- and anti-inflammatory reactions at distal versus proximal sites from the periodontal plaque, (C) 1999 Academic Press.