{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T23:23:36Z","timestamp":1769556216569,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Gerodontology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This paper describes the effect of <jats:italic>Porphyromonas gingivalis (P\u00a0gingivalis)<\/jats:italic> lipopolysaccharide (LPS) on the expression of interleukin\u20106 (IL\u20106) and C\u2010C motif chemokine ligand 2 (CCL2) in cultured hCMEC\/D3 human brain microvascular endothelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>P\u00a0gingivalis<\/jats:italic> is one of the important pathogens in periodontitis, and periodontitis is a risk factor for brain disorders including cerebrovascular diseases and Alzheimer's disease. However, the mechanisms underlying the pathogenesis of <jats:italic>P\u00a0gingivalis<\/jats:italic>\u2010mediated brain diseases are incompletely understood. Effects of <jats:italic>P\u00a0gingivalis<\/jats:italic> LPS on brain endothelial cells are not known well.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The hCMEC\/D3 human brain microvascular endothelial cells were cultured and treated with <jats:italic>P\u00a0gingivalis<\/jats:italic> LPS. The expression of IL\u20106 and CCL2 mRNA and protein was examined using quantitative reverse transcription\u2010polymerase chain reaction and enzyme\u2010linked immunosorbent assay, respectively. Effect of inhibitors of Toll\u2010like receptor (TLR) 2, TLR4, nuclear factor\u2010\u03baB (NF\u2010\u03baB), p38 mitogen\u2010activated protein kinase (MAPK) and c\u2010Jun N\u2010terminal kinase (JNK) was also investigated. Phosphorylation of NF\u2010\u03baB p65, p38 MAPK and JNK was examined using Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>P\u00a0gingivalis<\/jats:italic> LPS\u2010induced mRNA and protein expression of IL\u20106 and CCL2 in hCMEC\/D3 cells in a concentration\u2010dependent manner at the concentration of 0.5\u201050\u00a0\u00b5g\/mL. Maximal mRNA expression of IL\u20106 and CCL2 was found 2 and 4\u00a0hours after stimulation, respectively. Induction of IL\u20106 and CCL2 by <jats:italic>P\u00a0gingivalis<\/jats:italic> LPS was almost completely inhibited by pretreatment of cells with TLR4 inhibitor but not by TLR2 inhibitor. Treatment of cells with <jats:italic>P\u00a0gingivalis<\/jats:italic> LPS for up to 2\u00a0hours induced phosphorylation of NF\u2010\u03baB p65, p38 MAPK and JNK. IL\u20106 induction was decreased by pretreatment of cells with NF\u2010\u03baB inhibitor SN50 or p38 MAPK inhibitor SB203580, while CCL2 induction was reduced by SN50 or JNK inhibitor SP600125.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IL\u20106 and CCL2 produced upon <jats:italic>P\u00a0gingivalis<\/jats:italic> LPS stimulation may contribute to the inflammatory reactions in brain endothelial cells and subsequent neurological disorders such as cerebrovascular and Alzheimer's diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ger.12545","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T19:36:59Z","timestamp":1613849819000},"page":"139-147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["<i>Porphyromonas gingivalis<\/i> lipopolysaccharide induces interleukin\u20106 and c\u2010c motif chemokine ligand 2 expression in cultured hCMEC\/D3 human brain microvascular endothelial cells"],"prefix":"10.1111","volume":"39","author":[{"given":"Natsu","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Vascular Biology Institute of Brain Science Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology Institute of Brain Science Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shogo","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology Institute of Brain Science Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiko","family":"Seya","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology Institute of Brain Science 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