Porphyromonas gingivalis lipopolysaccharide promotes T-hel per17 cell differentiation by upregulating Delta-like ligand 4 expression on CD14+ monocytes

摘要

Backgroud. To investigate the effect and mechanism of Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) on Th17 cell differentiation mediated by CD14(+) monocytes. @@@ Methods. P. gingivalis LPS-activated CD14(+) monocytes were co-cultured with CD4(+)T cells in different cell ratios. An indirect co-culture system was also established using transwell chambers. Furthermore, anti-Delta-like ligand 4 (Dll-4) antibody was used to investigate the role of Dll-4 in Th17 cell response. The mRNA expression was analyzed using quantitative reverse transcription-polymerase chain reaction, and secreted cytokines in culture supernatant were detected using enzyme-linked immunosorbent assay. Flow cytometry was used to determine the frequencies of Th17 cells. IL-17 protein expression levels were determined using western blotting assay. @@@ Results. P. gingivalis LPS increased the expressions of interleukin (IL)-1 beta, IL-6, IL-23 and transforming growth factor (TGF)-beta in CD14(+) monocytes. Th17 cell frequency upregulated, which is not solely cytokine-dependent but rather requires cell-cell contact with activated monocytes, particularly in the 1:10 cell ratio. Furthermore, P. gingivalis LPS increased t he expression of Dll-4 on CD14(+) monocytes, whereas the anti-Dll-4 a ntibody decreased the response of Th17 cells. The results suggest that P. gingivalis LPS enhances Th17 cell response via Dll-4 upregulation on CD14(+) monocytes.

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