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Mol Oral Microbiol. 2018 Aug;33(4):292-299. doi: 10.1111/omi.12224. Epub 2018 May 2.

Tannerella forsythia-produced methylglyoxal causes accumulation of advanced glycation endproducts to trigger cytokine secretion in human monocytes.

Author information

1
Department of Oral Biology, School of Public Health and Health Related Professions, University at Buffalo, Buffalo, NY, USA.
2
Department of Biotechnical and Clinical Laboratory Sciences, School of Public Health and Health Related Professions, University at Buffalo, Buffalo, NY, USA.
3
Department of Epidemiology and Environmental Health, School of Public Health and Health Related Professions, University at Buffalo, Buffalo, NY, USA.

Abstract

The periodontal pathogen Tannerella forsythia has the unique ability to produce methylglyoxal (MGO), an electrophilic compound which can covalently modify amino acid side chains and generate inflammatory adducts known as advanced glycation endproducts (AGEs). In periodontitis, concentrations of MGO in gingival-crevicular fluid are increased and are correlated with the T. forsythia load. However, the source of MGO and the extent to which MGO may contribute to periodontal inflammation has not been fully explored. In this study we identified a functional homolog of the enzyme methylglyoxal synthase (MgsA) involved in the production of MGO in T. forsythia. While wild-type T.forsythia produced a significant amount of MGO in the medium, a mutant lacking this homolog produced little to no MGO. Furthermore, compared with the spent medium of the T. forsythia parental strain, the spent medium of the T. forsythia mgsA-deletion strain induced significantly lower nuclear factor-kappa B activity as well as proinflammogenic and pro-osteoclastogenic cytokines from THP-1 monocytes. The ability of T. forsythia to induce protein glycation endproducts via MGO was confirmed by an electrophoresis-based collagen chain mobility shift assay. Together these data demonstrated that T. forsythia produces MGO, which may contribute to inflammation via the generation of AGEs and thus act as a potential virulence factor of the bacterium.

KEYWORDS:

Tannerella forsythia ; AGEs; RAGE; methylglyoxal; periodontitis

PMID:
29573211
PMCID:
PMC6041129
[Available on 2019-08-01]
DOI:
10.1111/omi.12224
[Indexed for MEDLINE]

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