Institute of Dentistry, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
J Periodontal Res. 2015 Oct;50(5):650-7. doi: 10.1111/jre.12246. Epub 2014 Nov 29.
In periodontitis the host response to bacterial challenge includes activity of the multifunctional molecules adrenomedullin (AM) and nitric oxide (NO). The aim of this study was to investigate the role of periodontal bacteria in regulating the production of these molecules from cultured cells.
Regulation of AM and NO production from oral keratinocytes when challenged with culture supernatants from Aggregatibacter actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Veillonella atypica, Streptococcus salivarius and Candida albicans was examined. AM and NO were measured in cell culture supernatants using an enzyme-linked immunosorbent assay and the nitrate/nitrite (NO metabolites) Griess assay respectively. Cellular production of AM and inducible NO synthase was also analysed in target cells by immunofluorescence and Western blot analysis. The inter-relationship of AM and NO production were further investigated with macrophages.
A. actinomycetemcomitans and C. rectus induced maximal levels of both AM and NO after 6 and 48 h respectively from oral keratinocytes. AM production in macrophages was upregulated in response to the NO donor S-nitrosoglutathione and partially blocked by the inducible NO synthase inhibitor, N(ω) -Nitro-l-arginine methyl ester hydrochloride. Likewise, NO production was increased upon exposure to AM, while the AM receptor antagonist AM 22-52 reduced the release of NO.
Pathogens associated with aggressive periodontitis, A. actinomycetemcomitans and C. rectus, were more effective than those associated with chronic periodontitis, P. gingivalis and Prev. intermedia, and commensals, S. salivarius and V. atypica, as regards the upregulation of AM and NO production from oral keratinocytes. Interaction between these molecules was also demonstrated with macrophages. Understanding the coordinated regulation of AM and NO production in response to periodontal bacteria may identify ways to promote their protective effects and minimize destructive potential.
在牙周炎中，宿主对细菌挑战的反应包括多功能分子肾上腺髓质素（AM）和一氧化氮（NO）的活性。本研究旨在探讨牙周细菌在调节这些分子从培养细胞中产生的作用。
当用伴放线放线杆菌、直肠弯曲杆菌、核梭杆菌、牙龈卟啉单胞菌、中间普氏菌、非典型韦荣球菌、唾液链球菌和白色念珠菌的培养上清液刺激口腔角质形成细胞时，检测 AM 和 NO 产生的调节作用。使用酶联免疫吸附试验和硝酸盐/亚硝酸盐（NO 代谢物）Griess 测定法分别测量细胞培养上清液中的 AM 和 NO。通过免疫荧光和 Western blot 分析还分析了靶细胞中 AM 和诱导型一氧化氮合酶的细胞内产生。
伴放线放线杆菌和直肠弯曲杆菌分别在 6 和 48 小时后从口腔角质形成细胞中诱导出最大水平的 AM 和 NO。巨噬细胞中 AM 的产生通过一氧化氮供体 S-亚硝基谷胱甘肽而上调，并被诱导型一氧化氮合酶抑制剂 N（ω）-硝基-L-精氨酸甲酯盐酸盐部分阻断。同样，暴露于 AM 会增加 NO 的产生，而 AM 受体拮抗剂 AM 22-52 降低了 NO 的释放。
与侵袭性牙周炎相关的病原体，如伴放线放线杆菌和直肠弯曲杆菌，比与慢性牙周炎相关的病原体，如牙龈卟啉单胞菌和中间普氏菌，以及共生菌，如唾液链球菌和非典型韦荣球菌，更有效地调节口腔角质形成细胞中 AM 和 NO 的产生。还在巨噬细胞中证明了这些分子之间的相互作用。了解 AM 和 NO 产生对牙周细菌的协调调节，可能有助于确定促进其保护作用和最小化破坏性潜力的方法。
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