Modulation of host matrix metalloproteinases by bacterial virulence factors relevant in human periodontal diseases.
Modulation of host matrix metalloproteinases by bacterial virulence factors relevant in human periodontal diseases.
复制标题
与人类牙周病相关的细菌毒力因子对宿主基质金属蛋白酶的调节。
DOI：
10.1111/j.1601-0825.1995.tb00194.x
复制
发表时间：
2008
期刊：
影响因子：
3.8
通讯作者：
T. Sorsa
中科院分区：
文献类型：
--
作者：
Y. Ding;V. Uitto;J. Firth;T. Salo;M. Haapasalo;Y. Konttinen;T. Sorsa
目的
牙周病中的细菌病原体通过触发和诱导宿主细胞分泌基质金属蛋白酶（MMPs）来发挥其部分破坏作用。病原体分泌的磷脂酶（PLC）是一种细菌产物，可以触发这种宿主反应。本研究观察了外源性PLC对外周血中性粒细胞（PMNs）、体外培养的人牙龈上皮细胞和猪牙周膜上皮细胞释放、分泌和表达MMPs的影响。此外，PLC的活动在患病和健康的龈沟液（crevicular fluid，GCF）和明胶酶的分子形式存在于牙菌斑进行了研究。
材料和方法
分析GCF、唾液和牙菌斑样品的PLC和蛋白酶活性。用功能、免疫学和分子生物学方法检测PLC诱导中性粒细胞和口腔上皮细胞释放和表达MMPs的能力。
结果
PMN源性MMPs在牙周炎GCF和菌斑中占主导地位，成人牙周炎患者GCF中PLC活性高于健康对照组。纯化的细菌PLC（1 mU ml（-1））有效地诱导PMN脱颗粒。PLC还诱导培养的上皮细胞表达MMP。最强的反应是在MMP-9和MMP-2较少。在0.0 - 1.0 U ml（-1）PI-PLC的范围内，诱导作用呈剂量依赖性，静止期培养物比增殖期培养物更敏感。PLC诱导的MMP是极性的，MMP-9的水平增加的顶端区域和MMP-2的水平增加的基础方向分泌。北方分析显示MMP-9的mRNA水平显著增加，MMP-2和MMP-1的mRNA水平增加较小。在第二部分的研究中，我们调查的分子形式的MMPs释放牙周炎。在牙周炎患者的菌斑中，发现MMP-9转化为低分子量形式。从牙龈卟啉单胞菌（ATCC 33277）分离的蛋白酶能够将人proMMP转化为它们的活性形式。
结论
细菌PLC可诱导口腔黏膜上皮细胞PMN MMPs脱颗粒，增加MMPs的表达。释放的蛋白酶可以被菌斑细菌的蛋白酶转化为活性形式。因此，口腔致病菌可能间接参与牙周组织的破坏。
OBJECTIVE
Bacterial pathogens involved in periodontal diseases exert a part of their destructive effect by triggering and inducing host cells to elevate their secretion of matrix metalloproteinases (MMPs). Pathogen-secreted phospholipase (PLC) is one bacterial product that may trigger this host response. The roles of exogenous PLC leading to the release, secretion and expression of MMPs by peripheral blood neutrophils (PMNs), cultured epithelial cells of human gingiva and porcine periodontal ligament were investigated. Also the activities of PLC in the diseased and healthy gingival sulcular fluid (crevicular fluid, GCF) and molecular forms of gelatinases present in dental plaque were investigated.
MATERIALS AND METHODS
GCF, salivary and dental plaque samples were analyzed for PLC and proteinase activities. The abilities of PLC to induce PMNs and oral epithelial cells to release and express their MMPs were examined by specific functional, immunological and molecular biology means.
RESULTS
PMN-derived MMPs were found to predominate in periodontitis GCF and plaque, and PLC activities were higher in GCF of adult periodontitis patients than in healthy controls. Purified bacterial PLC (1 mU ml(-1)) efficiently induced PMN degranulation. PLC also induced MMP expression in the cultured epithelial cells. The strongest response was seen in MMP-9 and less in MMP-2. The induction was dose-dependent in the range of 0.0-1.0 U ml(-1) PI-PLC, and quiescent cultures were more responsive than proliferating ones. PLC induction of MMPs was polar, with increased levels of MMP-9 in the apical region and increased MMP-2 levels secreted in the basal direction. Northern analysis showed a strong increase in mRNA levels of MMP-9 and a smaller increase for MMP-2 and MMP-1. In the second part of the study we investigated the molecular forms of the released MMPs during periodontitis. In bacterial plaque of periodontitis patients the MMP-9 were found to be converted into lower molecular weight forms. Isolated proteinase from Porphyromonas gingivalis (ATCC 33277) was able to convert human proMMPs to their active forms.
CONCLUSION
Bacterial PLC may induce degranulation of PMN MMPs and increase MMP expression in oral epithelial cells. The released proteases can be converted into active form by the proteases of plaque bacteria. Thereby, the pathogenic oral bacteria may indirectly participate in the destruction of periodontal tissues.
DOI：
10.1016/s0021-9258(18)98977-5
发表时间：
1991-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Tuula Salo;J. Lyons;F. Rahemtulla;H. Birkedal-Hansen;Hannu Larjava
通讯作者：
Tuula Salo;J. Lyons;F. Rahemtulla;H. Birkedal-Hansen;Hannu Larjava
不稳定糖尿病患者龈沟液胶原酶的细胞来源和四环素抑制。
影响因子：
6.7
作者：
Sorsa,T;Ingman,T;Suomalainen,K;Halinen,S;Saari,H;Konttinen,YT;Uitto,VJ;Golub,LM
通讯作者：
Golub,LM