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

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.