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

• Main Authors: Browne, R.W (Author), Genco, R.J (Author), Honma, K. (Author), LaMonte, M. (Author), Li, M. (Author), Settem, R.P (Author), Shankar, M. (Author), Sharma, A. (Author), Xu, D. (Author)
• Format: Article
• Language: English
• Published: Blackwell Publishing Ltd 2018
• Subjects: advanced glycation end product; advanced glycation end product receptor; AGEs; Article; bacterial enzyme; bacterial load; bacterial strain; bacterial virulence; controlled study; cytokine; cytokine release; Cytokines; deletion mutant; gel mobility shift assay; Glycation End Products, Advanced; high mobility group B1 protein; human; human cell; Humans; immunogenicity; immunoglobulin enhancer binding protein; inflammation; Inflammation; interleukin 10; interleukin 1beta; interleukin 6; MAPK signaling; metabolism; methylglyoxal; methylglyoxal synthase; microbiology; mitogen activated protein kinase p38; monocyte; Monocytes; mutant; nonhuman; osteoclastogenesis; pathogenicity; periodontitis; Periodontitis; phosphatase; protein degradation; protein function; protein glycosylation; Pyruvaldehyde; RAGE; secreted embryonic alkaline phosphatase; stress activated protein kinase; synthetase; Tannerella forsythia; THP-1 cell line; THP-1 Cells; transcription factor AP 1; tumor necrosis factor; unclassified drug; virulence factor; Virulence Factors; wild type
• Online Access: View Fulltext in Publisher

 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. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd