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Epstein-Barr virus infection in chronically inflamed periapical granulomas.

Makino K, Takeichi O, Hatori K, Imai K, Ochiai K, Ogiso B - PLoS ONE (2015)

Bottom Line: In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10); the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001).Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER)-expressing cells.In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1) of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Endodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.

ABSTRACT
Periapical granulomas are lesions around the apex of a tooth caused by a polymicrobial infection. Treatment with antibacterial agents is normally performed to eliminate bacteria from root canals; however, loss of the supporting alveolar bone is typically observed, and tooth extraction is often selected if root canal treatment does not work well. Therefore, bacteria and other microorganisms could be involved in this disease. To understand the pathogenesis of periapical granulomas more precisely, we focused on the association with Epstein-Barr virus (EBV) using surgically removed periapical granulomas (n = 32). EBV DNA was detected in 25 of 32 periapical granulomas (78.1%) by real-time PCR, and the median number of EBV DNA copies was approximately 8,688.01/μg total DNA. In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10); the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001). Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER)-expressing cells. EBER was detected in the cytoplasm and nuclei of B cells and plasma cells in six of nine periapical granulomas, but not in healthy gingival tissues. In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1) of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells. These data suggest that B cells and plasma cells in inflamed granulomas are a major source of EBV infection, and that EBV could play a pivotal role in controlling immune cell responses in periapical granulomas.

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Related in: MedlinePlus

Specimens used in this study.(A) X-ray observation of periapical lesions caused at lower incisal teeth. Radiolucency around the apex showed alveolar bone resorption. (B) Periapical lesion surgically removed from a patient showing at (A).
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pone.0121548.g001: Specimens used in this study.(A) X-ray observation of periapical lesions caused at lower incisal teeth. Radiolucency around the apex showed alveolar bone resorption. (B) Periapical lesion surgically removed from a patient showing at (A).

Mentions: In total, 40 patients (9 males and 31 females; age range, 24–78 years) who were referred to the Department of Endodontics at Nihon University School of Dentistry Dental Hospital (Tokyo, Japan) because of persistent periapical periodontitis were included in this study. The clinical symptoms of the patients included an absence of throbbing pain, pain on palpation of the mucosa around the root apex, and percussion pain. An apparent radiolucency was seen around the root apex of all teeth (Fig 1A). Endodontic treatments had been applied several times by general practitioners; however, the patients were still experiencing symptoms. Therefore, endodontic surgery (apicoectomy and retrograde filling) was selected. Patients had no systemic diseases, and antibiotics have not been taken during the previous 6 months. This study was approved by the ethics committee of Nihon University School of Dentistry, based on the Declaration of Helsinki. Before sample collection, the experimental design, risks, and potential for discomfort were explained fully, and all patients signed consent forms.


Epstein-Barr virus infection in chronically inflamed periapical granulomas.

Makino K, Takeichi O, Hatori K, Imai K, Ochiai K, Ogiso B - PLoS ONE (2015)

Specimens used in this study.(A) X-ray observation of periapical lesions caused at lower incisal teeth. Radiolucency around the apex showed alveolar bone resorption. (B) Periapical lesion surgically removed from a patient showing at (A).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401687&req=5

pone.0121548.g001: Specimens used in this study.(A) X-ray observation of periapical lesions caused at lower incisal teeth. Radiolucency around the apex showed alveolar bone resorption. (B) Periapical lesion surgically removed from a patient showing at (A).
Mentions: In total, 40 patients (9 males and 31 females; age range, 24–78 years) who were referred to the Department of Endodontics at Nihon University School of Dentistry Dental Hospital (Tokyo, Japan) because of persistent periapical periodontitis were included in this study. The clinical symptoms of the patients included an absence of throbbing pain, pain on palpation of the mucosa around the root apex, and percussion pain. An apparent radiolucency was seen around the root apex of all teeth (Fig 1A). Endodontic treatments had been applied several times by general practitioners; however, the patients were still experiencing symptoms. Therefore, endodontic surgery (apicoectomy and retrograde filling) was selected. Patients had no systemic diseases, and antibiotics have not been taken during the previous 6 months. This study was approved by the ethics committee of Nihon University School of Dentistry, based on the Declaration of Helsinki. Before sample collection, the experimental design, risks, and potential for discomfort were explained fully, and all patients signed consent forms.

Bottom Line: In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10); the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001).Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER)-expressing cells.In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1) of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Endodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.

ABSTRACT
Periapical granulomas are lesions around the apex of a tooth caused by a polymicrobial infection. Treatment with antibacterial agents is normally performed to eliminate bacteria from root canals; however, loss of the supporting alveolar bone is typically observed, and tooth extraction is often selected if root canal treatment does not work well. Therefore, bacteria and other microorganisms could be involved in this disease. To understand the pathogenesis of periapical granulomas more precisely, we focused on the association with Epstein-Barr virus (EBV) using surgically removed periapical granulomas (n = 32). EBV DNA was detected in 25 of 32 periapical granulomas (78.1%) by real-time PCR, and the median number of EBV DNA copies was approximately 8,688.01/μg total DNA. In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10); the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001). Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER)-expressing cells. EBER was detected in the cytoplasm and nuclei of B cells and plasma cells in six of nine periapical granulomas, but not in healthy gingival tissues. In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1) of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells. These data suggest that B cells and plasma cells in inflamed granulomas are a major source of EBV infection, and that EBV could play a pivotal role in controlling immune cell responses in periapical granulomas.

Show MeSH
Related in: MedlinePlus