Possible immunomodulatory role of Filifactor alocis through beta-defensin 2 in gingival keratinocytes

Abstract

Objectives: The present study aimed to investigate a possible immunomodulatory role of the periodontopathogen Filifactor alocis through the antimicrobial peptide hBD-2 on the expression of chemokines in human gingival keratinocytes. Materials and methods: Cells were cultured in the presence or absence of periodontopathogenic bacteria, such as F. alocis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola, to evaluate the regulation of hBD-2, CXCL8 and CCL20. Furthermore, the cells were exposed or not to hBD-2 and the expression of CXCL8 and CCL20 and their receptors was evaluated. Results: All bacteria induced a significant upregulation of hBD-2, CXCL8, and CCL20 gene expressions. In addition, F. alocis significantly increased their protein levels, as detected by ELISA. Pre-incubation of the cells with the TLR2 inhibitor resulted in a significant downregulation of hBD-2 expression in F. alocis-treated cells. Gingival keratinocytes exposed to hBD-2 resulted in a significant and dose-dependent increase of all chemokines and their receptors. Conclusions: F. alocis increased the production of chemotactic cytokines, suggesting an increase in the recruitment of immunoinflammatory cells in periodontal diseases. The chemotaxis-promoting effect is partly direct, but is also mediated via hBD-2. F. alocis stimulates the synthesis of hBD-2, which in turn could promote the expression and synthesis of these chemokines and their receptors. In addition, hBD-2 has an autostimulatory effect and stimulates the synthesis of these chemokines, so that the chemotaxis triggered by F. alocis is further fueled. Clinical relevance: F. alocis and hBD-2 have a significant role in periodontitis, showing their importance for diagnostic and treatment approaches.