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Aggregatibacter actinomycetemcomitans regulates the expression of integrins and reduces cell adhesion via integrin α5 in human gingival epithelial cells

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Abstract

Gingival epithelial cells form a physiological barrier against bacterial invasion. Excessive bacterial invasion destroys the attachment between the tooth surface and the epithelium, resulting in periodontitis. Integrins play a significant role in cell attachment; therefore, we hypothesized that bacterial infection might decrease the expressions of these integrins in gingival epithelial cells, resulting in reduced cell adhesion. Immortalized human gingival epithelial cells were co-cultured with Aggregatibacter actinomycetemcomitans Y4 (Aa Y4), and the gene expression levels of IL-8, proliferating cell nuclear antigen (PCNA), and integrins (α2, α3, α5, β4, and β6) were measured using quantitative reverse transcription polymerase chain reaction. Expression of PCNA and integrins, except integrin α5, was significantly downregulated, while expression of IL-8 and integrin α5 was significantly upregulated in the cells co-cultured with Aa Y4. The number of adherent cells significantly decreased when co-cultured with Aa Y4, as determined using cell adhesion assays. In the cells co-cultured with Aa Y4 and an integrin α5 neutralizing antibody, there was no effect on the expression of IL-8 and PCNA, while the expressions of integrins α2, α3, β4, and β6, and the number of adherent cells did not decrease. The number of invading bacteria in the cells was reduced in the presence of the antibody and increased in the presence of TLR2/4 inhibitor. Therefore, integrin α5 might be involved in Aa Y4 invasion into gingival epithelial cells, and the resulting signal transduction cascade reduces cell adhesion by decreasing the expression of integrins, while the TLR2/4 signaling cascade regulates IL-8 expression.

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Acknowledgements

This study is supported by a Grant-in-Aid for Research Activity (Start-up Number: JP22890119) and a Grant-in-Aid for Young Scientists (B; Number: JP24792327). We would like to thank Editage (www.editage.jp) for English language editing.

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Authors and Affiliations

  1. Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Shinsuke Kochi, Keisuke Yamashiro, Shoichi Hongo, Yuki Ugawa, Masayuki Shimoe, Mari Kawamura, Chiaki Hirata-Yoshihara, Hidetaka Ideguchi & Shogo Takashiba

  2. Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan

    Tadashi Yamamoto

  3. Deparment of Endodontics, Osaka Dental University, Osaka, Japan

    Hiroshi Maeda

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  1. Shinsuke Kochi
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Correspondence to Shogo Takashiba.

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Kochi, S., Yamashiro, K., Hongo, S. et al. Aggregatibacter actinomycetemcomitans regulates the expression of integrins and reduces cell adhesion via integrin α5 in human gingival epithelial cells. Mol Cell Biochem 436, 39–48 (2017). https://doi.org/10.1007/s11010-017-3076-z

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