title: Mechanisms of Porphyromonas gingivalis-induced monocyte chemoattractant protein-1 expression in endothelial cells.
abstract: Monocyte chemoattractant protein-1 (MCP-1) is expressed in vascular endothelial cells of inflamed gingival tissues and plays an important role in periodontal pathogenesis. Endothelial cells produce high levels of MCP-1 in response to Porphyromonas gingivalis, an important periodontal pathogen. The present study investigated the mechanisms involved in MCP-1 production by human umbilical vein endothelial cells (HUVEC) following infection with P. gingivalis. In contrast to P. gingivalis, Bacteroides forsythus only weakly stimulated MCP-1 production while Treponema denticola could not induce MCP-1 in HUVEC. The MCP-1 production was independent of endogenous interleukin (IL)-1alpha as IL-1 receptor antagonist treatment did not reduce MCP-1 production by P. gingivalis. Meanwhile, antioxidant treatment and inhibition of NAD(P)H oxidase significantly reduced MCP-1 production. Pharmacological inhibition of p38 mitogen-associated protein (MAP) kinase, c-Jun N-terminal kinase (JNK), nuclear factor-kappaB (NF-kappaB) or activator protein-1 (AP-1) also substantially attenuated P. gingivalis-induced MCP-1 expression by HUVEC. Indeed, activation of NF-kappaB and AP-1 was observed in P. gingivalis-infected HUVEC. These results suggest that MCP-1 expression is upregulated in P. gingivalis-infected endothelial cells via reactive oxygen species, p38 MAP kinase, JNK, NF-kappaB, and AP-1.
authors.affiliation: Department of Oral Microbiology, Chonnam National University Dental School, 300 Yongbong-Dong, Puk-Gu, Kwangju 500-757, South Korea.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Choi
authors.forename: Sun-Ah
authors.initials: SA
authors.lastname: Park
authors.forename: Won-Mann
authors.initials: WM
authors.lastname: Oh
authors.forename: Ho-Cheol
authors.initials: HC
authors.lastname: Kang
authors.forename: Howard K
authors.initials: HK
authors.lastname: Kuramitsu
authors.forename: Byung-Gook
authors.initials: BG
authors.lastname: Kim
authors.forename: In-Chol
authors.initials: IC
authors.lastname: Kang
mesh_terms: D016866:Bacteroidaceae Infections / Q000209:etiology; D001439:Bacteroides / Q000472:pathogenicity; D001483:Base Sequence; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000235:genetics; D004730:Endothelium, Vascular / Q000382:microbiology; D015870:Gene Expression; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010518:Periodontitis / Q000209:etiology; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048373:Treponema denticola / Q000472:pathogenicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D004247:DNA; D009247:NADH, NADPH Oxidoreductases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases