Work

Effects of pro-inflammatory cytokines induced by Porphyromonas gingivalis on cell cycle regulation in brain endothelial cells

Year: 2025

Type: article

Abstract: OBJECTIVES: Advanced periodontitis potentially contributes to Alzheimer's disease (AD) development and progression by altering the blood-brain barrier microenvironment in the cerebral microvascular endothelium. This results, in cytotoxicity, cell cycle disruption, and increased pro-inflammatory cytokine expression, allowing pathogens to enter the brain and damage the central nervous system (CNS). This study evaluated the effects of Porphyromonas gingivalis W83 infection on pro-inflammatory response, cell viability, and cell cycle regulation in mouse brain endothelial cells (mBECs). METHODS: mBECs were stimulated with live P. gingivalis at different multiplicity of infection (MOI) values (1:5, 1:10, 1:50, 1:100, 1:200) for 6, 12, 24, and 48 h. Cell viability, cell cycle regulation, and pro-inflammatory cytokine mRNA expression were assessed using the alamarBlue assay, flow cytometry, and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively. RESULTS: P. gingivalis reduced cell viability, induced morphological changes in mBECs by >50 % after 48 h (p < 0.05) and caused concentration-dependent arrest in the S and G0/G1 phases of the cell cycle at MOI = 1:100 and 1:200. The Il6, Il1b, and tumor necrosis factor alpha (Tnf) mRNA expression increased significantly compared to that of the controls (p < 0.05). CONCLUSIONS: P. gingivalis reduced cellular metabolism and induced early cell cycle arrest at the G0/G1 phase in mBECs cells. It also increased the pro-inflammatory response, which could be associated with cell death and possible senescence of brain endothelial cells. These results suggested a possible role for P. gingivalis in the pathogenesis of AD. Further studies are required to elucidate these underlying mechanisms.

Source: Journal of Oral Biosciences

DOI: 10.1016/j.job.2025.100668

Authors: Andrea Fernanda Rodríguez, Juan Sebastian Buitrago, Yormaris Castillo, Gloria Inés Lafaurie, Diana Marcela Buitrago-Ramirez

Institution: Universidad El Bosque

Language: English

Topic: Oral microbiology and periodontitis research

Subfield: Periodontics

Field: Dentistry

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $2,950