Porphyromonas gingivalis enhances pneumococcal adhesion to human alveolar epithelial cells by increasing expression of host platelet-activating factor receptor.

Streptococcus pneumoniae causes pneumonia by infecting the alveolar epithelium via binding to host receptors, such as the platelet-activating factor receptor (PAFR). Although chronic periodontitis has been identified as a pneumonia risk factor, how periodontopathic bacteria cause pneumonia is not known. We found that S. pneumoniae adhered to PAFR expressed on A549 human alveolar epithelial cells stimulated by Porphyromonas gingivalis culture supernatant, and this was abrogated by a PAFR-specific inhibitor. Among the major virulence factors of P. gingivalis [lipopolysaccharide (LPS), fimbriae and gingipains (Rgps and Kgp)], PAFR expression and pneumococcal adhesion were executed in an Rgp-dependent manner. LPS and fimbriae did not induce PAFR expression. Hence, our findings suggest that P. gingivalis enhances pneumococcal adhesion to human alveoli by inducing PAFR expression and that gingipains are responsible for this.

The Periodontopathic Bacterium Fusobacterium nucleatum Induced Proinflammatory Cytokine Production by Human Respiratory Epithelial Cell Lines and in the Lower Respiratory Organs in Mice.

BACKGROUND/AIMS: The most prevalent infectious disease, chronic periodontitis which leads to alveolar bone destruction and subsequent tooth loss, develops due to proinflammatory cytokine production induced by periodontopathic bacteria. Chronic obstructive pulmonary disease (COPD), a non-infectious disease, is the third leading cause of death globally. This condition exacerbates frequently, and which is attributable to proinflammatory cytokine production induced by infection by respiratory microorganisms such as Streptococcus pneumoniae. Although a positive association has recently been revealed between chronic periodontitis and COPD, how periodontitis contributes to the pathogenesis of COPD remains unclear. Therefore, we hypothesized that some periodontopathic bacteria are involved in the exacerbation of COPD through the induction of proinflammatory cytokine production by respiratory epithelial cells. In this connection, COPD develops in the airways; however, because most periodontopathic bacteria are anaerobic, they are unlikely to exhibit stable virulence in the lower respiratory organs in humans. Hence, we aimed to elucidate whether exposure to heat-inactivated periodontopathic bacteria induces proinflammatory cytokine production by several human respiratory epithelial cell lines and in the lower respiratory organs and serum in mice. METHODS: Real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) were used to investigate in vitro induction by heat-inactivated periodontopathic bacteria and S. pneumoniae for mRNA expression and protein production of interleukin (IL)-8 and IL-6 by human respiratory epithelial cell lines. ELISA was also used to determine in vivo induction of cytokine production in the lower respiratory organs and serum of intratracheally heat-inactivated Fusobacterium nucleatum-inoculated mice. RESULTS: Some, but not all, periodontopathic bacteria, especially F. nucleatum, strongly induced IL-8 and IL-6 production by BEAS-2B bronchial epithelial cells. In addition, F. nucleatum induced IL-8 production by A549 alveolar epithelial cells as well as IL-8 and IL-6 production by Detroit 562 pharyngeal epithelial cells. Furthermore, F. nucleatum induced considerably higher cytokine production than S. pneumoniae. This was also observed in the entire lower respiratory organs and serum in mice. CONCLUSION: Exposure to increased number of F. nucleatum potentially induces proinflammatory cytokine production by human bronchial and pharyngeal epithelial cells, which may trigger exacerbation of COPD.

Diagnostic accuracy of lip force and tongue strength for sarcopenic dysphagia in older inpatients: A cross-sectional observational study.

BACKGROUND & AIMS: Dysphagia can be caused by sarcopenia in older adults. Although sarcopenic dysphagia has been reported to be associated with low tongue strength, whether tongue strength can be useful as a diagnostic index for sarcopenic dysphagia remains unclear. In addition, the association between sarcopenic dysphagia and lip force is unknown. The aim of the present study was to clarify the association of lip force and tongue strength with sarcopenic dysphagia, and their diagnostic accuracy for sarcopenic dysphagia. METHODS: A cross-sectional study was conducted in consecutive 245 (166 women) inpatients aged ≥65 years in the post-acute phase of illness. The presence of sarcopenic dysphagia, lip force, and tongue strength were assessed. Additional factors were also assessed: cognitive function, nutritional status, comorbidity, oral intake level, occlusion status, physical function, and inflammatory status. Multivariable logistic regression analysis was conducted with the presence of sarcopenic dysphagia as a dependent variable. Lip force and tongue strength were assessed with the area under the receiver operating characteristic curve (AUC) to clarify diagnostic accuracy for sarcopenic dysphagia. In addition, the cut-off values of lip force and tongue strength for identifying sarcopenic dysphagia were determined according to sex. RESULTS: In total, 86 patients (35.1%) had sarcopenic dysphagia. Both men and women with sarcopenic dysphagia had lower lip force and tongue strength than men and women without dysphagia or sarcopenic dysphagia (p < 0.001 for all). In multivariable logistic regression analysis, sarcopenic dysphagia was significantly associated with lip force (OR = 0.63, 95% CI 0.53-0.74, p < 0.001) and tongue strength (OR = 0.92, 95% CI 0.87-0.98, p = 0.011). The AUCs for lip force in patients with sarcopenic dysphagia were 0.88 (CI 0.81-0.95, p < 0.001) for men and 0.84 (CI 0.77-0.90, p < 0.001) for women. The AUCs for tongue strength were 0.79 (CI 0.69-0.89, p < 0.001) for men and 0.74 (CI 0.65-0.82, p < 0.001) for women. The cut-off values for sarcopenic dysphagia in men were 10.4 N for lip force and 24.3 kPa for tongue strength; the cut-off values in women were 8.5 N for lip force and 23.9 kPa for tongue strength. CONCLUSION: In older inpatients who are suspected as having dysfunction due to sarcopenia, lip force and tongue strength can be independently useful indices for diagnosing sarcopenic dysphagia, and may be factors that prevent and improve sarcopenic dysphagia.

Cynaropicrin from Cynara scolymus L. suppresses Porphyromonas gingivalis LPS-induced production of inflammatory cytokines in human gingival fibroblasts and RANKL-induced osteoclast differentiation in RAW264.7 cells.

Periodontal diseases are a major public health problem affecting over half of the adult population worldwide. Lipopolysaccharide (LPS) produced by the periodontopathic bacterium Porphyromonas gingivalis induces the expression of inflammatory cytokines that promote inflammatory bone destruction. Mounting evidence supports that periodontal diseases are involved in the onset and progression of several systemic diseases, such as aspiration pneumonia and diabetes. Although treatment of periodontal diseases by removing the periodontopathic bacteria by brushing is a standard practice, it has limitations and is not effective in all cases. Therefore, a new method to replace or complement brushing is needed for the treatment of periodontal diseases. In this study, we investigated the anti-inflammatory effects of an extract from Cynara scolymus L. and its pharmacologically effective compound cynaropicrin, a sesquiterpene lactone, on human gingival fibroblasts (HGFs) stimulated by LPS and the potential anti-osteoclastogenic effects on RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL). We found that cynaropicrin inhibited IL-8 and IL-6 mRNA and protein synthesis in LPS-stimulated HGFs in a dose-dependent manner. P. gingivalis LPS-induced degradation of IκBα and phosphorylation of NF-κB p65 were also suppressed by cynaropicrin, as was LPS-stimulated NF-κB transactivation. Thus, cynaropicrin's inhibition of P. gingivalis LPS-induced IL-8 and IL-6 expression may be due to the inhibition of the NF-κB pathway. Furthermore, we showed that cynaropicrin dramatically reduced RANKL-induced osteoclast differentiation. These results suggest that cynaropicrin may be useful for preventing periodontal diseases and could prove valuable in the development of more effective preventative approaches for periodontal diseases.