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Proteomic analysis of P. gingivalis-Lipopolysaccharide induced neuroinflammation in SH-SY5Y and HMC3 cells

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Abstract

Chronic periodontitis and its keystone pathogen, Porphyromonas gingivalis, have increasingly been linked with Alzheimer’s disease (AD). However, P.gingivalis-lipopolysaccharide (LPS) mediated release of neuroinflammatory proteins contributes to AD remains underexplored. In this study, we utilized data-independent acquisition mass spectrometry to characterize P.gingivalis-LPS induced profile of differentially expressed proteins associated with the neuroinflammatory response in human neuroblastoma (SH-SY5Y) and human microglial (HMC3) cells. We reported a set of 124 proteins in SH-SY5Y cells and 96 proteins in HMC3 cells whose levels were significantly upregulated or downregulated by exposure to P. gingivalis-LPS. Our findings demonstrate that P. gingivalis-LPS contributed to the elevated expressions of dementia biomarkers and pro-inflammatory cytokines that include APP, Aβ1–42, Aβ1–40, T-Tau, p-Tau, VEGF, TGF-β, IL-1β, IL-6 and TNF-α through 2 distinct pathways of extracellular sensing by cell surface receptors and intracellular cytosolic receptors. Interestingly, intracellular signaling proteins activated with P. gingivalis-LPS transfection using Lipofectamine™ 2000 had significantly higher fold change protein expression compared to the extracellular signaling with P. gingivalis-LPS treatment. Additionally, we also explored P. gingivalis-LPS mediated activation of caspase-4 dependent non canonical inflammasome pathway in both SH-SY5Y and HMC3 cells. In summary, P. gingivalis-LPS induced neuroinflammatory protein expression in SH-SY5Y and HMC3 cells, provided insights into the specific inflammatory pathways underlying the potential link between P. gingivalis-LPS infection and the pathogenesis of Alzheimer’s disease and related dementias.

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Data availability

The proteomics raw data are available through proteomeXchange MassIVE repository under MassIVE identifier MSV000093432.

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Acknowledgements

We thank Dr. Samuel G Mackintosh from the UAMS Proteomics Core for the use of their equipment’s and expertise. We are grateful to Ms. Amanda Pangle and Ms. Yingni Che for technical assistance. We are also thankful to Eric Rathman, MS, ELS from UAMS Scientific Communication Group for proofreading and editing the present manuscript.

Funding

This study was supported in part by the Claude D. Pepper Older American Independence Center grant (P30AG28718) from National Institute on Aging (NIA).

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Authors and Affiliations

  1. Department of Geriatrics, Donald W. Reynolds Institute On Aging, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR, 72205, USA

    Ambika Verma, Gohar Azhar, Pankaj Patyal, Xiaomin Zhang & Jeanne Y. Wei

  2. Department of Mathematics and Statistics, University of Arkansas at Little Rock, Little Rock, AR, USA

    Wei Zhang

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  1. Ambika Verma
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Contributions

AV, GA and JYW conceived the study. AV and PP performed the experiments. AV and PP wrote the manuscript with journalist input from GA and JYW. WZ analyzed the proteomic data. GA, XZ and JYW reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jeanne Y. Wei.

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Verma, A., Azhar, G., Patyal, P. et al. Proteomic analysis of P. gingivalis-Lipopolysaccharide induced neuroinflammation in SH-SY5Y and HMC3 cells. GeroScience (2024). https://doi.org/10.1007/s11357-024-01117-z

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