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Caveolin‐1 serves as a negative effector in senescent human gingival fibroblasts during Fusobacterium nucleatum infection
Author(s) -
Ahn S.H.,
Cho S.H.,
Song J.E.,
Kim S.,
Oh S.S.,
Jung S.,
Cho K.A.,
Lee T.H.
Publication year - 2017
Publication title -
molecular oral microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 77
eISSN - 2041-1014
pISSN - 2041-1006
DOI - 10.1111/omi.12167
Subject(s) - fusobacterium nucleatum , nadph oxidase , reactive oxygen species , caveolin 1 , biology , gene knockdown , mapk/erk pathway , downregulation and upregulation , proinflammatory cytokine , microbiology and biotechnology , phosphorylation , immunology , periodontitis , medicine , inflammation , biochemistry , porphyromonas gingivalis , gene
Summary 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 ( GF s) is critical to the development of periodontal diseases. However, the mechanisms underlying the age‐related infection of GF s by F. nucleatum remain unknown. We used young (fourth passage) and senescent (22nd passage) GF s to investigate the mechanisms of F. nucleatum infection in aged GF s and first observed increased invasion of F. nucleatum in senescent GF s. 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 GF s reduced F. nucleatum invasion. Additionally, F. nucleatum infection triggered the production of reactive oxygen species ( ROS ) through activation of NADPH oxidase in GF s, but senescent GF s exhibited significantly lower levels of NADPH oxidase activity and ROS production compared with young GF s in both the uninfected and infected conditions. Also, senescent GF s 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 GF s 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 GF s.