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Tannerella forsythia-produced methylglyoxal causes accumulation of advanced glycation endproducts to trigger cytokine secretion in human monocytes.
Molecular Oral Microbiology ( IF 3.7 ) Pub Date : 2018-05-02 , DOI: 10.1111/omi.12224
R P Settem 1 , K Honma 1 , M Shankar 2 , M Li 1 , M LaMonte 3 , D Xu 1 , R J Genco 1 , R W Browne 2 , A Sharma 1
Affiliation  

The periodontal pathogen Tannerella forsythia has the unique ability to produce methylglyoxal (MGO), an electrophilic compound which can covalently modify amino acid side chains and generate inflammatory adducts known as advanced glycation endproducts (AGEs). In periodontitis, concentrations of MGO in gingival‐crevicular fluid are increased and are correlated with the T. forsythia load. However, the source of MGO and the extent to which MGO may contribute to periodontal inflammation has not been fully explored. In this study we identified a functional homolog of the enzyme methylglyoxal synthase (MgsA) involved in the production of MGO in T. forsythia. While wild‐type T.forsythia produced a significant amount of MGO in the medium, a mutant lacking this homolog produced little to no MGO. Furthermore, compared with the spent medium of the T. forsythia parental strain, the spent medium of the T. forsythia mgsA‐deletion strain induced significantly lower nuclear factor‐kappa B activity as well as proinflammogenic and pro‐osteoclastogenic cytokines from THP‐1 monocytes. The ability of T. forsythia to induce protein glycation endproducts via MGO was confirmed by an electrophoresis‐based collagen chain mobility shift assay. Together these data demonstrated that T. forsythia produces MGO, which may contribute to inflammation via the generation of AGEs and thus act as a potential virulence factor of the bacterium.

中文翻译:

坛花连翘产生的甲基乙二醛引起高级糖基化终产物的积累,从而触发人单核细胞中细胞因子的分泌。

牙周病原体坦氏菌连翘具有产生甲基乙二醛(MGO)的独特能力,MGO是一种可以共价修饰氨基酸侧链并产生称为高级糖化终产物(AGEs)的炎症加合物的亲电化合物。在牙周炎中,龈沟液中MGO的浓度增加,并且与连翘负荷有关。但是,尚未充分探讨MGO的来源以及MGO可能导致牙周炎症的程度。在这项研究中,我们确定了参与连翘的MGO生产的甲基乙二醛合酶(MgsA)的功能同源物。野生型连翘在培养基中产生大量的MGO,缺少该同源物的突变体几乎没有产生MGO。此外,与连翘的亲代培养基的废培养基相比,连翘的mgsA缺失菌株的废培养基诱导了THP-1单核细胞的核因子κB活性以及促炎和破骨细胞生成因子的显着降低。 。基于电泳的胶原链迁移率移动测定法证实了连翘通过MGO诱导蛋白质糖基化终产物的能力。这些数据一起证明,连翘产生MGO,其可能通过AGEs的产生而导致炎症,从而成为细菌的潜在毒力因子。
更新日期:2018-05-02
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