Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis
Abstract Background 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 pres...
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doaj-b1b548b5f8904dbe978d82cf495aef2b2020-11-24T21:34:40ZengBMCJournal of Translational Medicine1479-58762018-07-0116111410.1186/s12967-018-1588-2Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitisMarianne Engström0Kaja Eriksson1Linkiat Lee2Monika Hermansson3Anders Johansson4Anthony P. Nicholas5Natalija Gerasimcik6Karin Lundberg7Lars Klareskog8Anca Irinel Catrina9Tülay Yucel-Lindberg10Rheumatology Unit, Department of Medicine, Karolinska InstitutetDepartment of Dental Medicine, Karolinska InstitutetDepartment of Dental Medicine, Karolinska InstitutetRheumatology Unit, Department of Medicine, Karolinska InstitutetDivision of Molecular Periodontology, Department of Odontology, Umeå UniversityDepartment of Neurology, University of Alabama at Birmingham and Birmingham VA Medical CenterDepartment of Dental Medicine, Karolinska InstitutetRheumatology Unit, Department of Medicine, Karolinska InstitutetRheumatology Unit, Department of Medicine, Karolinska InstitutetRheumatology Unit, Department of Medicine, Karolinska InstitutetDepartment of Dental Medicine, Karolinska InstitutetAbstract Background 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. Methods 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12967-018-1588-2Aggregatibacter actinomycetemcomitansCitrullinated proteinsGingival tissueInflammationLeukotoxinPeptidylarginine deiminases |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marianne Engström Kaja Eriksson Linkiat Lee Monika Hermansson Anders Johansson Anthony P. Nicholas Natalija Gerasimcik Karin Lundberg Lars Klareskog Anca Irinel Catrina Tülay Yucel-Lindberg |
spellingShingle |
Marianne Engström Kaja Eriksson Linkiat Lee Monika Hermansson Anders Johansson Anthony P. Nicholas Natalija Gerasimcik Karin Lundberg Lars Klareskog Anca Irinel Catrina Tülay Yucel-Lindberg Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis Journal of Translational Medicine Aggregatibacter actinomycetemcomitans Citrullinated proteins Gingival tissue Inflammation Leukotoxin Peptidylarginine deiminases |
author_facet |
Marianne Engström Kaja Eriksson Linkiat Lee Monika Hermansson Anders Johansson Anthony P. Nicholas Natalija Gerasimcik Karin Lundberg Lars Klareskog Anca Irinel Catrina Tülay Yucel-Lindberg |
author_sort |
Marianne Engström |
title |
Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis |
title_short |
Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis |
title_full |
Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis |
title_fullStr |
Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis |
title_full_unstemmed |
Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis |
title_sort |
increased citrullination and expression of peptidylarginine deiminases independently of p. gingivalis and a. actinomycetemcomitans in gingival tissue of patients with periodontitis |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2018-07-01 |
description |
Abstract Background 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. Methods 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. Results 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. Conclusion 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. |
topic |
Aggregatibacter actinomycetemcomitans Citrullinated proteins Gingival tissue Inflammation Leukotoxin Peptidylarginine deiminases |
url |
http://link.springer.com/article/10.1186/s12967-018-1588-2 |
work_keys_str_mv |
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