Treponema denticola suppresses expression of human {beta}-defensin-3 in gingival epithelial cells through inhibition of the toll-like receptor 2 axis.
We reported previously that Treponema denticola, one of the periodontal pathogens, suppresses the expression of human beta-defensins (HBDs) in human gingival epithelial cells. To identify the mechanisms involved in this suppression, immortalized and normal human gingival epithelial cells were infected with live or heat-killed T. denticola for 24 h, and then the expression of HBDs was examined by real-time RT-PCR. Live T. denticola suppressed the expression of HBD-3 substantially and also suppressed the expression of HBD-1 and HBD-2. However, heat-killed bacteria did not produce a suppressive effect but instead slightly upregulated the levels of HBD-2 and HBD-3. In contrast to live T. denticola, which reduced the activation of mitogen-activated protein kinase (MAPK) and NF-kappaB within an hour of infection, heat-killed bacteria did not show any inhibitory effect on the MAPK and NF-kappaB signaling pathways. Knockdown of Toll-like receptor 2 (TLR2) via RNA interference abolished the suppressive effect of T. denticola on the expression of HBD-3. Heat-killed T. denticola but not live bacteria could activate TLR2 in CHO/CD14/TLR2 reporter cells, suggesting that T. denticola contains a heat-labile inhibitor(s) of TLR2 in addition to ligands recognized by TLR2. Indeed, live T. denticola was able to inhibit TLR2 activation by Pam(3)CSK. In conclusion, T. denticola suppressed the expression of HBD-3 by inhibiting the TLR2 axis in gingival epithelial cells. These results may provide new insight into the pathogenesis of periodontitis caused by T. denticola.
Shin
Ji Eun
JE
Department of Oromaxillofacial Infection & Immunity, School of Dentistry and Dental Research Institute, Seoul National University, 28-2 Yeongeon-dong, Jongno-gu, Seoul 110-749, South Korea.
Kim
Young Sook
YS
Oh
Ju-Eun
JE
Min
Byung-Moo
BM
Choi
Youngnim
Y
D002469:Cell Separation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D005434:Flow Cytometry; D005881:Gingiva / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D048373:Treponema denticola / Q000276:immunology; D014211:Treponemal Infections / Q000276:immunology*; D023083:beta-Defensins / Q000096:biosynthesis / Q000276:immunology
C422950:DEFB103A protein, human; D034741:RNA, Small Interfering; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D023083:beta-Defensins