Caveolin-1 serves as a negative effector in senescent human gingival fibroblasts during Fusobacterium nucleatum infection.
It is well established that aging is associated with increased susceptibility to infectious diseases. Fusobacterium nucleatum is a well-known bacterial species that plays a central bridging role between early and late colonizers in the human oral cavity. Further, the ability of F. nucleatum to invade gingival fibroblasts (GFs) is critical to the development of periodontal diseases. However, the mechanisms underlying the age-related infection of GFs by F. nucleatum remain unknown. We used young (fourth passage) and senescent (22nd passage) GFs to investigate the mechanisms of F. nucleatum infection in aged GFs and first observed increased invasion of F. nucleatum in senescent GFs. We also found that the co-localization of caveolin-1 (Cav-1), a protein marker of aging, with F. nucleatum and the knockdown of Cav-1 in GFs reduced F. nucleatum invasion. Additionally, F. nucleatum infection triggered the production of reactive oxygen species (ROS) through activation of NADPH oxidase in GFs, but senescent GFs exhibited significantly lower levels of NADPH oxidase activity and ROS production compared with young GFs in both the uninfected and infected conditions. Also, senescent GFs exhibited a decline in proinflammatory cytokine production and extracellular signal regulated kinase (ERK) phosphorylation following F. nucleatum infection. Interestingly, the knockdown of Cav-1 in senescent GFs increased NADPH oxidase activity and caused the upregulation of interleukin-6 and interleukin-8 and the phosphorylation of ERK. Collectively, the increased expression of Cav-1 might play a critical role in F. nucleatum invasion and could hinder the host response in senescent GFs.
Department of Oral Biochemistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Korea.
S H
SH
Ahn
Department of Molecular Medicine (BK21plus), Chonnam National University Graduate School, Gwangju, Korea.
S-H
SH
Cho
Department of Molecular Medicine (BK21plus), Chonnam National University Graduate School, Gwangju, Korea.
J-E
JE
Song
Department of Oral Biochemistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Korea.|Department of Molecular Medicine (BK21plus), Chonnam National University Graduate School, Gwangju, Korea.
S
S
Kim
Department of Oral Biochemistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Korea.
S S
SS
Oh
Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju, Korea.
S
S
Jung
Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea.
K A
KA
Cho
Department of Oral Biochemistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Korea.|Department of Molecular Medicine (BK21plus), Chonnam National University Graduate School, Gwangju, Korea.
T-H
TH
Lee
D051242:Caveolin 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016922:Cellular Senescence; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology*; D005881:Gingiva / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D010510:Periodontal Diseases / Q000382:microbiology; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
C495540:CAV1 protein, human; C508606:CXCL8 protein, human; D051242:Caveolin 1; D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D048052:Mitogen-Activated Protein Kinase 3

Fusobacterium nucleatum
; Caveolin-1; NADPH oxidase; gingival fibroblast; proinflammatory cytokines; senescence