Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis.
Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis.
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在牙周炎患者的牙龈组织中独立于牙龈疟原虫和放线菌的柠檬氨酸脱依酶的柠檬化和表达增加。
DOI：
10.1186/s12967-018-1588-2
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发表时间：
2018-07-31
影响因子：
7.4
通讯作者：
Yucel-Lindberg T
中科院分区：
文献类型：
--
作者：
Engström M;Eriksson K;Lee L;Hermansson M;Johansson A;Nicholas AP;Gerasimcik N;Lundberg K;Klareskog L;Catrina AI;Yucel-Lindberg T
类风湿性关节炎 (RA) 和牙周炎之间存在关联，这一发现表明类风湿性关节炎 (RA) 患者容易患晚期牙周炎，反之亦然。为了寻找这两种疾病可能的共同发病特征，我们研究了牙周炎个体和健康对照的牙周组织中瓜氨酸蛋白的存在和内源性肽基精氨酸脱亚胺酶（PAD2和PAD4）的表达，与牙周病原体牙龈卟啉单胞菌（P.gingivalis）和伴放线聚合杆菌（A. actinomycetemcomitans)，产生白细胞毒素作为毒力因子。这两种口腔细菌被认为与 RA 患者的抗瓜氨酸蛋白抗体有关。对 15 名牙周炎患者和 15 名无牙周病患者进行牙龈组织活检。通过免疫组织化学分析 CD3 阳性淋巴细胞、瓜氨酸蛋白、PAD2、PAD4、牙龈卟啉单胞菌以及放线放线菌和溶血曼海姆菌产生的白细胞毒素的存在，然后进行三盲半定量分析。曼-惠特尼和费舍尔的精确检验用于分析组间差异。通过 RT-qPCR 评估 PADI2 和 PADI4 mRNA 水平，并使用 Wilcoxon 符号秩检验进行分析。与健康牙龈组织（27%，4/15）相比，牙周炎受试者的牙龈结缔组织（80%，12/15）中观察到瓜氨酸蛋白染色增加，而牙龈上皮中没有观察到差异。牙周炎患者牙龈结缔组织中瓜氨酸酶 PAD2 和 PAD4 的染色也增加，而在两组牙龈上皮中观察到相似的 PAD2 和 PAD4 水平。同样，与健康对照相比，牙周炎患者牙龈组织中 PADI2 和 PADI4 的 mRNA 水平也有所增加。此外，来自患有和未患有牙周炎的不同研究个体的上皮和结缔组织中牙龈卟啉单胞菌和白细胞毒素的存在是相当的，并且牙周病原体的存在与瓜氨酸蛋白或PAD酶的表达之间没有相关性。慢性牙龈炎症与牙周炎中局部瓜氨酸化以及 PAD2 和 PAD4 表达增加有关。然而，牙周炎中瓜氨酸化以及 PAD2 和 PAD4 表达的增加与牙周病原体牙龈卟啉单胞菌和伴放线菌白毒素的存在无关。本文的在线版本 (10.1186/s12967-018-1588-2) 包含补充材料，可供授权用户使用。
A relationship between rheumatoid arthritis (RA) and periodontitis has been suggested from findings that individuals with RA are prone to have advanced periodontitis and vice versa. In search of possible common pathogenetic features of these two diseases, we investigated the presence of citrullinated proteins and expression of endogenous peptidylarginine deiminases (PAD2 and PAD4), in periodontal tissue of individuals with periodontitis and healthy controls, in relation to the periodontal pathogens Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), producing leukotoxin as virulence factor. These two oral bacteria have been suggested to be linked to anti-citrullinated protein antibodies in patients with RA. Gingival tissue biopsies were obtained from 15 patients with periodontitis and 15 individuals without periodontal disease. Presence of CD3-positive lymphocytes, citrullinated proteins, PAD2, PAD4, P. gingivalis as well as A. actinomycetemcomitans and Mannheimia haemolytica produced leukotoxins were analysed by immunohistochemistry, followed by triple-blind semi-quantitative analysis. Mann–Whitney and Fisher’s exact tests were used to analyse differences between groups. PADI2 and PADI4 mRNA levels were assessed by RT-qPCR and analysed using Wilcoxon signed rank test. Increased staining of citrullinated proteins was observed in gingival connective tissue from subjects with periodontitis (80%, 12/15) compared to healthy gingival tissue (27%, 4/15), whereas no differences were observed in gingival epithelium. There was also an increased staining of the citrullinating enzymes PAD2 and PAD4 in gingival connective tissue of patients with periodontitis whereas similar levels of PAD2 and PAD4 were observed in the gingival epithelium of the two groups. Similarly, the mRNA levels of PADI2 and PADI4 were also increased in the gingival tissue of patients with periodontitis compared to healthy controls. Furthermore, presence of P. gingivalis and leukotoxins was comparable in both epithelium and connective tissue, from the different investigated individuals with and without periodontitis, and there were no correlations between the presence of periodontal pathogens and the expression of citrullinated proteins or PAD enzymes. Chronic gingival inflammation is associated with increased local citrullination and PAD2 and PAD4 expression in periodontitis. The increased citrullination and PAD2 and PAD4 expression in periodontitis were, however, independent of the presence of periodontal pathogen P. gingivalis and A. actinomycetemcomitans leukotoxin. The online version of this article (10.1186/s12967-018-1588-2) contains supplementary material, which is available to authorized users.
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影响因子：
3.4
作者：
Laugisch, Oliver;Wong, Alicia;Sroka, Aneta;Kantyka, Tomasz;Koziel, Joanna;Neuhaus, Klaus;Sculean, Anton;Venables, Patrick J.;Potempa, Jan;Moeller, Burkhard;Eick, Sigrun
通讯作者：
Eick, Sigrun
影响因子：
3.5
作者：
Harvey, G. P.;Fitzsimmons, T. R.;Bartold, P. M.
通讯作者：
Bartold, P. M.
影响因子：
7.3
作者：
Fuggle NR;Smith TO;Kaul A;Sofat N
通讯作者：
Sofat N
影响因子：
4.3
作者：
Eke PI;Dye BA;Wei L;Slade GD;Thornton-Evans GO;Borgnakke WS;Taylor GW;Page RC;Beck JD;Genco RJ
通讯作者：
Genco RJ
影响因子：
13.6
作者：
Lamont RJ;Hajishengallis G
通讯作者：
Hajishengallis G