Prucsi, Z.; Zimny, A.; Płonczyńska, A.; Zubrzycka, N.; Potempa, J.; Sochalska, M. Porphyromonas gingivalis Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis. Int. J. Mol. Sci.2023, 24, 12922.
Prucsi, Z.; Zimny, A.; Płonczyńska, A.; Zubrzycka, N.; Potempa, J.; Sochalska, M. Porphyromonas gingivalis Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis. Int. J. Mol. Sci. 2023, 24, 12922.
Prucsi, Z.; Zimny, A.; Płonczyńska, A.; Zubrzycka, N.; Potempa, J.; Sochalska, M. Porphyromonas gingivalis Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis. Int. J. Mol. Sci.2023, 24, 12922.
Prucsi, Z.; Zimny, A.; Płonczyńska, A.; Zubrzycka, N.; Potempa, J.; Sochalska, M. Porphyromonas gingivalis Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis. Int. J. Mol. Sci. 2023, 24, 12922.
Abstract
Periodontitis is a widely spread chronic inflammatory disease caused by a changed oral microbiome. Although multiple species and risk factors have been associated with periodontitis, Porphyromonas gingivalis undoubtedly stands in the center as a keystone pathogen. The immune-modulatory function of P. gingivalis has been well characterized, but the mechanism by which peptidyl arginine deiminase (PPAD), a citrullinating enzyme, contributes to the infinite loop of inflammation is not fully understood. To determine the functional role of hypercitrullination in the context of periodontitis, we performed a comparative analysis on neutrophils stimulated by the wild type and the PPAD mutant strain that lacks an active enzyme. Our flow cytometric analysis revealed that PPAD contributes to the prolonged neutrophil survival upon bacteria stimulation, which was accompanied by aberrant IL-6 and TNF-α secretion in the experimental environment. To further elaborate on the complex mechanism by which citrullination sustains the chronic inflammatory state, we assessed the ROS production and phagocytic activity of neutrophils. Flow cytometry and colony formation assay demonstrated that PPAD obstructs the resolution of inflammation by promoting neutrophil survival and the release of pro-inflammatory cytokines while making the bacteria itself more resilient to phagocytosis.
Biology and Life Sciences, Immunology and Microbiology
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