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Mice exposed to a novel environment show hyperlocomotion that is inhibited by systemic administration of LPS derived from <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>Ec<\/jats:italic>-LPS). However, whether <jats:italic>Pg<\/jats:italic>-LPS influences novelty-induced locomotion is unknown. Accordingly, we carried out an open field test to analyse the effects of <jats:italic>Pg<\/jats:italic>-LPS. For comparison, effects of <jats:italic>Ec<\/jats:italic>-LPS were also studied. We additionally investigated the influence of systemic administration of <jats:italic>Pg<\/jats:italic>-LPS or <jats:italic>Ec<\/jats:italic>-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 <jats:italic>Pg<\/jats:italic>-LPS may block TLR4 <jats:italic>in vitro<\/jats:italic>, we analysed the effects of <jats:italic>Pg<\/jats:italic>-LPS on <jats:italic>Ec<\/jats:italic>-LPS-induced changes in behavioural and biochemical parameters. Male ddY mice were used. <jats:italic>Pg<\/jats:italic>- or <jats:italic>Ec<\/jats:italic>-LPS and TAK-242 were administered intraperitoneally. <jats:italic>Ec<\/jats:italic>-LPS (840 \u03bcg\/kg), but not <jats:italic>Pg<\/jats:italic>-LPS (100, 500 and 840 \u03bcg\/kg), inhibited novelty-induced locomotion, which was antagonized by TAK-242 (3.0 mg\/kg). <jats:italic>Ec<\/jats:italic>-LPS (840 \u03bcg\/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 <jats:italic>Ec<\/jats:italic>-LPS-induced increases in TNF-alpha levels in blood. <jats:italic>Pg<\/jats:italic>-LPS (100, 500, and 840 \u03bcg\/kg) did not alter blood IL-6, TNF-alpha, or IL-10 levels. The <jats:italic>Ec<\/jats:italic>-LPS-induced increase in blood IL-10, but not IL-6 and TNF-alpha, levels was inhibited by <jats:italic>Pg<\/jats:italic>-LPS (500 \u03bcg\/kg). These results suggest that TLR4 stimulation mediates the inhibition of novel environment-induced locomotion in mice following systemic administration of <jats:italic>Ec<\/jats:italic>-LPS, while also increasing blood IL-6 and IL-10 levels. In contrast, <jats:italic>Pg<\/jats:italic>-LPS did not exhibit these effects. The present study also provides <jats:italic>in vivo<\/jats:italic> evidence that <jats:italic>Pg<\/jats:italic>-LPS can inhibit TLR4-mediated increases in blood levels of IL-10, a cytokine thought to prevent the development of periodontal disease.<\/jats:p>","DOI":"10.1371\/journal.pone.0292830","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T17:30:26Z","timestamp":1718040626000},"page":"e0292830","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli: Differential and interactive effects on novelty-induced hyperlocomotion, blood cytokine levels and TLR4-related processes"],"prefix":"10.1371","volume":"19","author":[{"given":"Yuri","family":"Aono","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kawashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arata","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4964-1656","authenticated-orcid":true,"given":"Tetsuro","family":"Kono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Hashizume-Takizawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Okada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Kosuge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenobu","family":"Senpuku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L.","family":"Waddington","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6325-9616","authenticated-orcid":true,"given":"Tadashi","family":"Saigusa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"key":"pone.0292830.ref001","doi-asserted-by":"crossref","first-page":"28788","DOI":"10.3402\/jom.v7.28788","article-title":"Invasion of Porphyromonas gingivalis strains into vascular cells and tissue","volume":"7","author":"I Olsen","year":"2015","journal-title":"J. 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