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Aim: Blood–brain barrier (BBB) disorder is one of the early findings in cognitive impairments. We have recently found that Porphyromonas gingivalis bacteraemia can cause cognitive impairment and increased BBB permeability. This study aimed to find out the possible key virulence factors of P. gingivalis contributing to the pathological process. Materials and Methods: C57/BL6 mice were infected with P. gingivalis or gingipains or P. gingivalis lipopolysaccharide (P. gingivalis LPS group) by tail vein injection for 8 weeks. The cognitive behaviour changes in mice, the histopathological changes in the hippocampus and cerebral cortex, the alternations of BBB permeability, and the changes in Mfsd2a and Cav‐1 levels were measured. The mechanisms of Ddx3x‐induced regulation on Mfsd2a by arginine‐specific gingipain A (RgpA) in BMECs were explored. Results: P. gingivalis and gingipains significantly promoted mice cognitive impairment, pathological changes in the hippocampus and cerebral cortex, increased BBB permeability, inhibited Mfsd2a expression and up‐regulated Cav‐1 expression. After RgpA stimulation, the permeability of the BBB model in vitro increased, and the Ddx3x/Mfsd2a/Cav‐1 regulatory axis was activated. Conclusions: Gingipains may be one of the key virulence factors of P. gingivalis to impair cognition and enhance BBB permeability by the Ddx3x/Mfsd2a/Cav‐1 axis. [ABSTRACT FROM AUTHOR]

Objectives: This paper aims to study the effect of the active form of vitamin D (calcitriol) on the internalized Porphyromonas gingivalis in macrophages and to assess the role of autophagy during this process. Materials and methods: Quantitative RT‐PCR and bacteria culture were used to quantify live P. gingivalis internalized into U937‐derived macrophages. Western blot assays were performed to detect the effect of P. gingivalis and calcitriol on autophagy in macrophages. Transmission electron microscope was used to observe the effect of calcitriol on the status of internalized P. gingivalis. Colocalization of P. gingivalis with the autophagosome and lysosome markers was observed by confocal laser scanning microscopy. Results: Calcitriol caused a dose‐dependent decrease in live P. gingivalis numbers and promoted both the endogenous and P. gingivalis‐induced autophagy in macrophages. Calcitriol significantly promoted the destruction of P. gingivalis and the colocalization of P. gingivalis with autophagosome and lysosome markers. Conversely, with 3‐MA, live P. gingivalis numbers in macrophages increased significantly and inhibition effect of calcitriol on the number of live P. gingivalis was attenuated. Conclusion: In U937‐derived macrophages, calcitriol may promote colocalization of P. gingivalis with autophagosomes and lysosomes, namely autophagy process, to degrade live P. gingivalis. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to explore the effects of the active form of vitamin D (calcitriol, 1α,25-dihydroxyvitamin D3 , 1α,25 (OH)2 D3 , 1,25D) on live Porphyromonas gingivalis internalized into KB cells and U937 cells.Methods: Quantitative real-time polymerase chain reaction method was used to evaluate the number of surviving P. gingivalis internalized into KB cells and U937 cells. Transmission electron microscopy was used to detect P. gingivalis in cells. A western blot analysis was performed to observe LC3 expressions.Results: 1) Treatment with 1,25D decreased the number of live P. gingivalis in KB cells and U937 cells in a dose-dependent manner. 2) Dividing P. gingivalis were found only in KB cells but not in U937 cells. The cell walls of most P. gingivalis in KB cells were intact, while those in U937 cells were disrupted. Treatment with 1,25D promoted the encapsulation of P. gingivalis in autophagosomes in both KB and U937 cells. 3) Both 1,25D treatment and P. gingivalis infection increased the LC3 II/I ratio. Furthermore, 1,25D treatment increased the P. gingivalis-upregulated LC3 II/I ratio. 4) Treatment with 3-methyladenine (3-MA) decreased the number of P. gingivalis by 11.41% in KB cells, while increased that by 121.51% in U937 cells. Under 1,25D treatment conditions, 3-MA treatment increased the number of P. gingivalis by 88.71% in KB cells and by 284.70% in U937 cells.Conclusions: Autophagy may facilitate P. gingivalis survival in KB cells and eliminate P. gingivalis in U937 cells. Treatment with 1,25D may help decrease the number of live P. gingivalis in KB cells and U937 cells by promoting functional autophagy. [ABSTRACT FROM AUTHOR]