Journal Article

Lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli: Differential and interactive effects on novelty-induced hyperlocomotion, blood cytokine levels and TLR4-related processes

Waddington, John L., Kawashima, Hiroki, Kono, Tetsuro, Okada, Hiroyuki, Kosuge, Yasuhiro, Saigusa, Tadashi, Senpuku, Hidenobu, Watanabe, Arata, Saito, Koji, Hashizume-Takizawa, Tomomi, Aono, Yuri

2024

Overview

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 additionally 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. Pg - or Ec -LPS and TAK-242 were administered intraperitoneally. Ec -LPS (840 μg/kg), but not Pg -LPS (100, 500 and 840 μg/kg), inhibited novelty-induced locomotion, which was antagonized by TAK-242 (3.0 mg/kg). Ec -LPS (840 μg/kg) increased blood levels of IL-6 and IL-10, which were 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 μg/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 μg/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 levels of IL-10, a cytokine thought to prevent the development of periodontal disease.

• Publisher: Public Library of Science
• Subject: Analysis / Animals / B cells / Behavior / Biology and Life Sciences / Blood / Blood levels / Cell walls / Cytokines / Cytokines - blood / Cytokines - metabolism / E coli / Escherichia coli / Experiments / Field tests / Flow cytometry / In vivo methods and tests / Interleukin 10 / Interleukin 6 / Interleukin-10 - blood / Interleukin-6 - blood / Lipopolysaccharides / Locomotion / Locomotion - drug effects / Male / Medicine and Health Sciences / Mice / Novelty / Open-field behavior / Periodontal disease / Periodontal diseases / Porphyromonas gingivalis / Social Sciences / Spleen / Sulfonamides / TLR4 protein / Toll-Like Receptor 4 - metabolism / Toll-like receptors / Tumor necrosis factor / Tumor Necrosis Factor-alpha - blood / Tumor necrosis factor-TNF / Vehicles