Lipopolysaccharides derived fromPorphyromonas gingivalisandEscherichia coli:differential and interactive effects on novelty-induced hyperlocomotion, blood cytokine levels and TRL4-related processes

Abstract

AbstractLipopolysaccharide (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 fromEscherichia coli(Ec-LPS). However, whetherPg-LPS influences novelty-induced locomotion is unknown. Accordingly, we carried out an open field test to analyse the effects ofPg-LPS. For comparison, effects ofEc-LPS were also studied. We also investigated the influence of systemic administration ofPg-LPS orEc-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. SincePg-LPS may block TLR4in vitro, we analysed the effects ofPg-LPS onEc-LPS-induced changes in behavioural and biochemical parameters. Male ddY mice were used. Compounds were administered intraperitoneally.Ec-LPS (840 µg/kg), but notPg-LPS (100, 500 and 840 µg/kg), inhibited novelty-induced locomotion, which was reversed by TAK-242 (3.0 mg/kg).Ec-LPS (840 µg/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 inhibitEc-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. TheEc-LPS-induced increase in blood IL-10, but not IL-6 and TNF-alpha, levels was inhibited byPg-LPS (500 µg/kg). These results suggest that TLR4 stimulation mediates the inhibition of novel environment-induced locomotion in mice following systemic administration ofEc-LPS, while also increasing blood IL-6 and IL-10 levels. In contrast,Pg-LPS did not exhibit these effects. The present study also providesin vivoevidence thatPg-LPS can inhibit TLR4-mediated increases in blood IL-10 levels, which is thought to prevent the development of periodontal disease.