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bioRxiv · 10.1101/2023.10.02.560531

Lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli: differential and interactive effects on novelty-induced hyperlocomotion, blood cytokine levels and TRL4-related processes

SAIGUSA, T.·Saito, K.·Aono, Y.·Watanabe, A.·Kono, T.·Hashizume-Takizawa, T.·Okada, H.·Kosuge, Y.·Senpuku, H.·Waddington, J. L.
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Abstract

Lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, activates Toll-like receptors (TLRs). Porphyromonas gingivalis (Pg) may be involved in the progression of periodontal disease. Mice exposed to a novel environment show hyperlocomotion that is inhibited by systemic administration of LPS derived from Escherichia coli (Ec-LPS). However, whether Pg-LPS influences novelty-induced locomotion is unknown. Accordingly, we carried out an open field test to analyse the effects of Pg-LPS. For comparison, effects of Ec-LPS were also studied. We also investigated the influence of systemic administration of Pg-LPS or Ec-LPS on IL-6, TNF-alpha, and IL-10 levels in blood, as they could be involved in the changes in locomotion. The TLR4 receptor antagonist TAK-242 was used to study the involvement of TLR4. Since Pg-LPS may block TLR4 in vitro, we analysed the effects of Pg-LPS on Ec-LPS-induced changes in behavioural and biochemical parameters. Male ddY mice were used. Compounds were administered intraperitoneally. Ec-LPS (840 {micro}g/kg), but not Pg-LPS (100, 500 and 840 {micro}g/kg), inhibited novelty-induced locomotion, which was reversed by TAK-242 (3.0 mg/kg). Ec-LPS (840 {micro}g/kg) increased blood levels of IL-6 and IL-10, which was antagonized by TAK-242 (3.0 mg/kg). However, TAK-242 did not inhibit Ec-LPS-induced increases in TNF-alpha levels in blood. Pg-LPS (100, 500, and 840 {micro}g/kg) did not alter blood IL-6, TNF-alpha, or IL-10 levels. The Ec-LPS-induced increase in blood IL-10, but not IL-6 and TNF-alpha, levels was inhibited by Pg-LPS (500 {micro}g/kg). These results suggest that TLR4 stimulation mediates the inhibition of novel environment-induced locomotion in mice following systemic administration of Ec-LPS, while also increasing blood IL-6 and IL-10 levels. In contrast, Pg-LPS did not exhibit these effects. The present study also provides in vivo evidence that Pg-LPS can inhibit TLR4-mediated increases in blood IL-10 levels, which is thought to prevent the development of periodontal disease.

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SAIGUSA, T., Saito, K., Aono, Y., Watanabe, A., Kono, T., Hashizume-Takizawa, T., Okada, H., Kosuge, Y., Senpuku, H., Waddington, J. L.. 2023-10-02. Lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli: differential and interactive effects on novelty-induced hyperlocomotion, blood cytokine levels and TRL4-related processes. https://doi.org/10.1101/2023.10.02.560531

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