Xylitol, an Anticaries Agent, Exhibits Potent Inhibition of Inflammatory Responses in Human THP‐1‐Derived Macrophages Infected With Porphyromonas gingivalis

Abstract

Background Xylitol is a well-known anticaries agent and has been used for the prevention and treatment of dental caries. In this study, the anti-inflammatory effects of xylitol are evaluated for possible use in the prevention and treatment of periodontal infections. Methods Cytokine expression was stimulated in THP-1 (human monocyte cell line)-derived macrophages by live Porphyromonas gingivalis, and enzyme-linked immunosorbent assay and a commercial multiplex assay kit were used to determine the effects of xylitol on live P. gingivalis–induced production of cytokine. The effects of xylitol on phagocytosis and the production of nitric oxide were determined using phagocytosis assay, viable cell count, and Griess reagent. The effects of xylitol on P. gingivalis adhesion were determined by immunostaining, and costimulatory molecule expression was examined by flow cytometry. Results Live P. gingivalis infection increased the production of representative proinflammatory cytokines, such as tumor necrosis factor-α and interleukin (IL)-1β, in a multiplicity of infection– and time-dependent manner. Live P. gingivalis also enhanced the release of cytokines and chemokines, such as IL-12 p40, eotaxin, interferon γ–induced protein 10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1. The pretreatment of xylitol significantly inhibited the P. gingivalis– induced cytokines production and nitric oxide production. In addition, xylitol inhibited the attachment of live P. gingivalis on THP-1-derived macrophages. Furthermore, xylitol exerted anti-phagocytic activity against both Escherichia coli and P. gingivalis. Conclusion These findings suggest that xylitol acts as an antiinflammatory agent in THP-1-derived macrophages infected with live P. gingivalis, which supports its use in periodontitis.

Aggregatibacter actinomycetemcomitans‐Induced AIM2 Inflammasome Activation Is Suppressed by Xylitol in Differentiated THP‐1 Macrophages

“…The authors of the present study reported on the anti‐inflammatory effect of xylitol suppressing IL‐1β and TNF‐α expression induced by P. gingivalis LPS in RAW 264.7 cells and the inhibitory effect on P. gingivalis growth 23 . Xylitol inhibited: 1) growth; 2) metabolism; and 3) polysaccharide production of mutans streptococci 22 , 24 . It was also recently found that xylitol inhibited IL‐1β and TNF‐α production through inhibition of internalization and phagocytosis of live P. gingivalis into differentiated THP‐1 macrophages and attachment of P. gingivalis to the surface of differentiated THP‐1 macrophages 24 .…”

“…Xylitol is a widely used anticaries agent because it is not fermented by Streptococcus mutans 22 , 24 , 50 . The authors of the present study reported on the anti‐inflammatory effect of xylitol suppressing IL‐1β and TNF‐α expression induced by P. gingivalis LPS in RAW 264.7 cells and the inhibitory effect on P. gingivalis growth 23 .…”

“…Xylitol inhibited: 1) growth; 2) metabolism; and 3) polysaccharide production of mutans streptococci 22 , 24 . It was also recently found that xylitol inhibited IL‐1β and TNF‐α production through inhibition of internalization and phagocytosis of live P. gingivalis into differentiated THP‐1 macrophages and attachment of P. gingivalis to the surface of differentiated THP‐1 macrophages 24 . In the present study, 3% xylitol was used, which was not cytotoxic to differentiated THP‐1 macrophages as in the previous study.…”

“…Xylitol also has an anti‐inflammatory effect, and has previously been reported to inhibit expression of TNF‐α and IL‐1β induced by Porphyromonas gingivalis 23 . It has also been demonstrated that xylitol suppressed expression of various cytokines and chemokines in differentiated macrophages infected with live P. gingivalis 24 . However, effect of xylitol on inflammasome activation induced by A. actinomycetemcomitans infection has not been investigated.…”

The role of probiotic bacteria in managing periodontal disease: a systematic review

“…Xylitol, a naturally occurring a low-calorie pentose sugar substitute, is known for its ability to suppress growth and metabolism of cariogenic mutans streptococci in particular [45]. However, a little known effect of xylitol is its ability to launch an anti-inflammatory response in macrophages infected with the periodontopathogen P gingivalis [46,47]. Shimauchi et al [31] evaluated this phenomenon, and they did not find any significant improvement in clinical parameters of periodontitis between the control group (placebo + xylitol) and the test group (probiotic + xylitol).…”