Treponema denticola suppresses expression of human beta-defensin-2 in gingival epithelial cells through inhibition of TNFalpha production and TLR2 activation.
We previously reported that Treponema denticola, a periodontal pathogen, suppressed the expression of human beta-defensins (HBDs) and IL-8 in human gingival epithelial cells. To clarify the receptor(s) involved in the suppression of HBD-2, immortalized gingival epithelial (HOK-16B) cells were infected with live or heat-killed T. denticola for 24 h, and the expression of HBD-2 was examined by real-time RT-PCR. Live T. denticola, but not heat-killed bacteria, suppressed the expression of HBD-2 about 40%. Time courses of suppression revealed that T. denticola suppressed HBD-2 expression only at late time points, which was accompanied with the suppression of TNFalpha production. Neutralization of TNFalpha with an antibody abrogated the suppressive effect of T. denticola on HBD-2. Accordingly, heat-killed T. denticola did not suppress TNFalpha production. Knock-down of toll-like receptor (TLR) 2 via RNA interference reversed the suppressive effect of T. denticola on the expression of HBD-3, but not on the production of TNFalpha. Collectively, T. denticola suppresses the expression of HBD-2 in gingival epithelial cells by inhibiting the TLR2 axis and TNFalpha production, which may contribute to the pathogenesis of periodontitis by T. denticola.
Shin
Ji Eun
JE
Department of Oromaxillofacial Infection and Immunity, Brain Korea 21 CLS, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 110-749, Korea.
Choi
Youngnim
Y
D001428:Bacterial Vaccines / Q000276:immunology; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D015870:Gene Expression; D005881:Gingiva / Q000166:cytology; D054884:Host-Pathogen Interactions; D006801:Humans; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D048373:Treponema denticola / Q000254:growth & development* / Q000276:immunology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism
D001428:Bacterial Vaccines; C106641:DEFB4A protein, human; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins