Porphyromonas gingivalis promote microglia M1 polarization through the NF-кB signaling pathway

Xue Li; Chao Yao; Dongmei Lan; Yurong Chen; Yan Wang; Shengcai Qi

Heliyon (Aug 2024)

Porphyromonas gingivalis promote microglia M1 polarization through the NF-кB signaling pathway

Xue Li,
Chao Yao,
Dongmei Lan,
Yurong Chen,
Yan Wang,
Shengcai Qi

Affiliations

Xue Li: Department of Oral Prosthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200002, China; Medical College, Anhui University of Science and Technology, Huainan, 232001, China
Chao Yao: Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200002, China
Dongmei Lan: Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200002, China
Yurong Chen: Department of Oral Prosthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200002, China; Medical College, Anhui University of Science and Technology, Huainan, 232001, China
Yan Wang: Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200002, China; Medical College, Anhui University of Science and Technology, Huainan, 232001, China; Department of Preventive Dentistry, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200000, China; Corresponding author. Development of Preventive Dentistry, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200000, China.
Shengcai Qi: Department of Oral Prosthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200002, China; Medical College, Anhui University of Science and Technology, Huainan, 232001, China; Corresponding author. Department of Prosthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China.

Journal volume & issue: Vol. 10, no. 15
p. e35340

Abstract

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Background: Porphyromonas gingivalis (P.gingivalis) is associated with the onset of Alzheimer's disease (AD), but the underlying molecular mechanism is unclear. Neuroinflammation in the brain from the microglial immune response induces the pathological progression of AD. In this study, the roles and molecular mechanism of P.gingivalis in microglial inflammation in vitro were investigated. Methods: In this study, a P.gingivalis oral administration mouse model was generated, and microglia were stimulated with P.gingivalis in vitro. The viability of the microglia after P.gingivalis treatment was evaluated through CCK-8 and live/dead cell staining. Inflammation in brain tissue after P.gingivalis treatment and the immune response of microglia in vitro were detected by RT‒PCR, Western blotting and IF. Moreover, the RNA sequence was used, and the role of the NF-κB signalling pathway in microglial activation was analysed after P.gingivalis stimulation. Results: The mRNA and protein levels of IL-6 and IL-17 were increased, and the expression of IL-10 was decreased in brain tissue after P.gingivalis oral administration. The viability of the HMC3 cells significantly decreased with 5% P.gingivalis after stimulation. The results of live/dead cell staining also showed the inhibitory effect of 5% P.gingivalis supplementation on cell viability. Moreover, 5% P.gingivalis supplementation increased the mRNA and protein levels of IL-6 and IL-17 and decreased IL-10 expression in HMC3 cells. P.gingivalis supplementation increased the mRNA and protein levels of iNOS and CD86 and decreased CD206 expression in HMC3 cells. RNA sequencing revealed that the NF-κB signalling pathway was involved in this process. Furthermore, p-P65 was upregulated and p-IKBα was downregulated in brain tissue and HMC3 cells after P.gingivalis stimulation, and an NF-κB signalling pathway inhibitor (QNZ) reversed the viability, M1 polarization and inflammatory factors of microglia in HMC3 cells in vitro. Conclusions: In conclusion, P.gingivalis induced neuroinflammation in the brain, possibly through promotion of M1 polarization of microglia via activation of the NF-κB signalling pathway during the progression of AD.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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