The score for each paw ranged from 0 (no swelling) to 4 (erythema and severe swelling encompassing the ankle and foot); the scores for all four paws were summed to generate a representative arthritis score

The score for each paw ranged from 0 (no swelling) to 4 (erythema and severe swelling encompassing the ankle and foot); the scores for all four paws were summed to generate a representative arthritis score. between normal, CIA control mice and mice infected with W83 or (F.n).(TIF) pone.0188698.s002.tif (1.4M) GUID:?3BD213E4-421F-4648-8373-A425B478FEDF S1 File: ARRIVE guidelines checklist. Experiments were performed according to the ARRIVE guidelines.(PDF) pone.0188698.s003.pdf (1.0M) GUID:?8E213D31-AE43-42E6-9630-80FEC81537AC Data Availability StatementAll relevant data are within the paper and its Supporting Information files. Abstract Epidemiological studies show an association between rheumatoid arthritis (RA) and periodontal disease. (on autoimmune arthritis exacerbated arthritis score in CIA mice. Synovial inflammation and bone destruction in CIA mice infected with were more severe than in uninfected CIA mice. Both W83 and 2561 strains were more pro-arthritic after arthritis symptom was fully activated. Interestingly, only W83 strain was arthritogenic before autoimmune reaction initiated. Citrullination was detected in synovial tissue of CIA mice and CIA mice inoculated with exacerbated disease in a mouse model of autoimmune arthritis and increased the expression of citrullinated antigens in the synovium. The arthritogenic effects of were at least in part, dependent upon the bacterial strain with or without fimbriae expression, route and time of infection. (PPAD) is the only active form of bacterial PAD [22]. (is usually found in oral cavities, which induce periodontal disease such as periodontitis [9]. The physiological role of PPAD is yet not known, however, it was suggested to enhance the bacterial survival by producing ammonia during deamination [23]. Ammonia neutralizes the acidic condition in the periodontal pocket and optimizes gingipain and PPAD function which induce ATP production and negatively regulate the neutrophil function [24]. Because of these characteristics, the CP-640186 relation between and host peptides citrullinated by PPAD act as autoantigens that exacerbate autoimmune responses associated with RA [28C31]. Several isotopic forms of PAD in and humans are reported [22,32,33]. PAD2 and PAD4 expression was shown in the rheumatoid synovium and synovial fluid cells [20,34,35]. PAD4 was present in the synovial fluid of RA patients and patients with spondyloathropathy or OA. On the other hand, PAD2 was expressed in the knee joint of RA patients, but not in OA patients [33]. It was also shown that the PAD expression in the synovium tissue correlated with infiltration of inflammatory cells, synovial thickening, and synovium vascularity [20]. Based on these observations, we aimed to examine the pathogenic role of in autoimmune arthritis. The arthritogenic effects of was confirmed by bacterial strain (i.e. W83 and 2561), route, and time point of inoculation. We conducted clinical and histological analyses of a collagen-induced arthritis (CIA) mouse model infected with showed increased expression of enolase, fibronectin, and citrullinated antigens in the synovial region. This study may provide a possible link between and RA. Materials and methods Ethical approval All procedures involving CP-640186 animals were performed in accordance with the Laboratory Animals Welfare Act, the Guide for the Care and Use of Laboratory Animals, and the Guidelines CP-640186 and Policies for Rodent Experimentation provided by the Institutional Animal Care and Use Committee of the School of Medicine of The Catholic University of Korea. Experiments were performed according to the ARRIVE guidelines LRP1 [9]. The study protocol was approved by the Institutional Review Board of The Catholic University of Korea (CUMC-2013-0011-02). Synovial samples from patients with RA were obtained from the Catholic Human Disease Sample Bank. Samples were donated anonymously; therefore, the requirement for consent was waived by the Institutional Review Board. Induction and assessment of collagen-induced arthritis Mice were each subdivided into 6 groups. Each group was composed of 5 mice. Non-treated mice were used as normal control group. To induce CIA, mice were immunized intradermally using 2mg/mL Bovine type II collagen (CII; Chondrex, Redmond, WA, USA) emulsified 1:1 with 2mg/mL Complete Freunds adjuvant (CFA; Chondrex, Redmond, WA, USA). 6-week-old male DBA/1J mice (Orient Bio, Seongnam, Korea) were intradermally injected at day 0 with 100mL of CII/CFA emulsion. CII emulsified 1:1 with Incomplete Freunds adjuvant (IFA; Chondrex, Redmond, WA, USA) was injected into mice.