Toll-Like Receptor 2 and NALP2 Mediate Induction of Human Beta-Defensins byFusobacterium nucleatumin Gingival Epithelial Cells
- 1 March 2009
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 77 (3), 1044-1052
- https://doi.org/10.1128/iai.00449-08
Abstract
We previously reported that infection byFusobacterium nucleatumstrongly induced the expression of both human beta-defensin 2 (HBD-2) and HBD-3 by gingival epithelial cells. The aim of this study was to characterize the pattern recognition receptors (PRRs) and regulatory mechanisms involved in the induction of HBD-2 and -3 expression byF. nucleatumin gingival epithelial cells. Immortalized human gingival epithelial HOK-16B cells were infected with live or heat-killedF. nucleatum, and the expression of HBDs and interleukin-8 (IL-8) was examined by real-time reverse transcription-PCR and enzyme-linked immunosorbent assay, respectively. Live, but not heat-killed,F. nucleatuminvaded HOK-16B cells, as seen by confocal microscopy and flow cytometry. LiveF. nucleatuminduced both HBD-2 and -3 efficiently, whereas heat-killed bacteria induced only HBD-3 at a reduced level. Knockdown of NACHT-LRR- and pyrin domain-containing protein 2 (NALP2), the most abundant intracellular PRR in HOK-16B cells, by RNA interference (RNAi) significantly reduced the induction of HBD-3 but not HBD-2 and IL-8. In addition, knockdown of Toll-like receptor 2 (TLR2) by RNAi reduced the upregulation of HBD-2 and -3 but not IL-8. Heat-killedF. nucleatumwas hindered in its ability to activate TLR2 and JNK signaling pathways. Theses data show that TLR2 and NALP2 mediate the induction of HBDs byF. nucleatumin gingival epithelial cells, but thresholds for the two HBD genes are different.Keywords
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