Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis.
Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis.
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DOI：
10.1186/ar4376
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发表时间：
2013-11-12
影响因子：
4.9
通讯作者：
Giannobile WV
中科院分区：
文献类型：
--
作者：
Marchesan JT;Gerow EA;Schaff R;Taut AD;Shin SY;Sugai J;Brand D;Burberry A;Jorns J;Lundy SK;Nuñez G;Fox DA;Giannobile WV
临床研究表明，牙周病(PD)对已确诊的类风湿性关节炎(RA)患者的血清炎症标志物和疾病评估有直接影响。然而，帕金森病对关节炎发展的影响尚不清楚。本研究采用胶原诱导性关节炎(CIA)模型，研究慢性PD在免疫激活和关节炎症发展中的作用。用完全弗氏佐剂(CFA)和不完全弗氏佐剂(IFA)乳化的II型胶原蛋白(CII)诱导DBA1/J小鼠感染牙龈卟啉单胞菌。通过爪部肿胀的视觉评分、爪部卡尺测量、mRNA表达、爪部微型计算机断层扫描(Micro-CT)分析、组织学和破骨细胞检测(TRAP)阳性的抗酒石酸酸性磷酸酶(TRAP)免疫组织化学方法评估关节炎的发展。检测血清和活化的脾细胞中细胞因子的表达。诱发帕金森病和/或关节炎的小鼠出现牙周病，表现为牙槽骨减少，牙龈组织和下颌下淋巴结的mRNA表达与对照组相比发生了变化。口腔感染牙龈假单胞菌可增加CFA/CII免疫小鼠的足爪肿胀和破骨细胞数量。在接受IFA/CII免疫的小鼠中，牙龈假单胞菌增加了关节炎的发病率和严重性。在感染牙周炎的小鼠中，观察到IFA/CII免疫后，爪部滑膜炎、骨侵蚀和破骨细胞数量增加。此外，细胞因子分析显示，在接受CFA/CII或IFA/CII免疫的小鼠中，当牙龈假单胞菌感染时，血清Th17/Th1比率有增加的趋势。口腔感染引起的细胞因子显著增加主要与活化的脾细胞Th17相关细胞因子有关，包括IL-1β、IL-6和IL-22，IL-1β、肿瘤坏死因子-α、转化生长因子-β、IL-6和IL-23。在关节炎诱导之前，慢性牙龈假单胞菌口腔感染会增加免疫系统的激活，有利于Th17细胞的反应，最终加速关节炎的发展。这些结果表明，慢性口腔感染可能主要通过激活Th17相关途径来影响RA的发展。
Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model. DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund’s adjuvant (CFA) or incomplete Freund’s adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression. Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group. Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.
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影响因子：
30.5
作者：
通讯作者：
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Keystone-Pathogen假设。
DOI：
10.1038/nrmicro2873
发表时间：
2012-10
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Chung, Whasun O.;An, Jonathan Y.;Yin, Lei;Hacker, Beth M.;Rohani, Maryam G.;Dommisch, Henrik;DiJulio, Dennis H.
通讯作者：
DiJulio, Dennis H.
影响因子：
--
作者：
Barck, KH;Lee, WP;Carano, RAD
通讯作者：
Carano, RAD
影响因子：
4.4
作者：
Burns, Elia;Bachrach, Gilad;Nussbaum, Gabriel
通讯作者：
Nussbaum, Gabriel