title: NOX1/2 activation in human gingival fibroblasts by Fusobacterium nucleatum facilitates attachment of Porphyromonas gingivalis.
abstract: Periodontal diseases are infectious polymicrobial inflammatory diseases that lead to destruction of the periodontal ligament, gingiva, and alveolar bone. Sequential colonization of a broad range of bacteria, including Fusobacterium nucleatum and Porphyromonas gingivalis, is an important phenomenon in this disease model. F. nucleatum is a facultative anaerobic species thought to be a key mediator of dental plaque maturation due to its extensive coaggregation with other oral bacteria, while P. gingivalis is an obligate anaerobic species that induces gingival inflammation by secreting various virulence factors. The formation of a bacterial complex by these two species is central to the pathogenesis of periodontal disease. Reactive oxygen species (ROS) are produced during bacterial infections and are involved in intracellular signaling. However, the impact of oral bacteria-induced ROS on the ecology of F. nucleatum and P. gingivalis has yet to be clarified. In the present study, we investigated ROS production induced in primary human oral cells by F. nucleatum and P. gingivalis and its effect on the formation of their bacterial complexes and further host cell apoptosis. We found that in primary human gingival fibroblasts (GFs), two NADPH oxidase isoforms, NOX1 and NOX2, were activated in response to F. nucleatum infection but not P. gingivalis infection. Accordingly, increased NADPH oxidase activity and production of superoxide anion were observed in GFs after F. nucleatum infection, but not after P. gingivalis infection. Interestingly, in NOX1, NOX2, or NOX1/NOX2 knockdown cells, the number of P. gingivalis decreased when the cells were coinfected with F. nucleatum. A similar pattern of host cell apoptosis was observed. This implies that F. nucleatum contributes to attachment of P. gingivalis by triggering activation of NADPH oxidase in host cells, which may provide an environment more favorable to strict anaerobic bacteria and have a subsequent effect on apoptosis of host cells.
authors.affiliation: Department of Oral Biochemistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Department of Molecular Medicine (BK21plus), Graduate School, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Song
authors.affiliation: Department of Molecular Medicine (BK21plus), Graduate School, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Suhee
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine (BK21plus), Graduate School, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Department of Oral Biochemistry, School of Dentistry, Chosun University, Gwangju, Republic of Korea.
authors.forename: Yun Kyong
authors.initials: YK
authors.lastname: Lim
authors.affiliation: Department of Oral Biochemistry, School of Dentistry, Chosun University, Gwangju, Republic of Korea.
authors.forename: Joong-Ki
authors.initials: JK
authors.lastname: Kook
authors.affiliation: Department of Oral and Maxillofacial Surgery, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Min-Suk
authors.initials: MS
authors.lastname: Kook
authors.affiliation: Department of Oral Biochemistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea. thlee83@jnu.ac.kr.|Department of Molecular Medicine (BK21plus), Graduate School, Chonnam National University, Gwangju, Republic of Korea. thlee83@jnu.ac.kr.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Lee
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016967:Fusobacterium nucleatum / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010510:Periodontal Diseases / Q000382:microbiology / Q000473:pathology*; D016966:Porphyromonas gingivalis / Q000378:metabolism* / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C056558:CYBB protein, human; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C402799:NOX1 protein, human
keywords: Fusobacterium nucleatum; Gingival fibroblast; NADPH oxidase; NOX1; NOX2; Porphyromonas gingivalis