Phenol/water extract of Treponema socranskii subsp. socranskii as an antagonist of Toll-like receptor 4 signalling.
Treponema socranskii is one of the most frequently found oral spirochaetes in periodontitis and endodontic infections. LPS or glycolipids from bacteria are potent stimulators of innate immune and inflammatory systems. In this study the bioactivity of a phenol/water extract from T. socranskii subsp. socranskii (TSS-P) was analysed. TSS-P showed minimal endotoxicity and no inducing potential for proinflammatory cytokines (TNF-alpha and IL-8) or for intercellular adhesion molecule-1 (ICAM-1) in human monocyte cell line THP-1 cells and primary cultured human gingival fibroblasts. Rather, it inhibited ICAM-1 expression and IL-8 secretion from cells stimulated by the LPS of Escherichia coli and Actinobacillus actinomycetemcomitans, which are known to be Toll-like receptor 4 (TLR4) agonists. However, this antagonistic activity was not shown in cells stimulated by peptidoglycan or IL-1beta. As its antagonistic mechanism, TSS-P blocked the binding of E. coli LPS to LPS-binding protein (LBP) and CD14, which are molecules involved in the recruitment of LPS to the cell membrane receptor complex TLR4-MD-2 for the intracellular signalling of LPS. TSS-P itself did not bind to MD-2 or THP-1 cells, but inhibited the binding of E. coli LPS to MD-2 or to the cells in the presence of serum (which could be replaced by recombinant human LBP and recombinant human CD14). The results suggest that TSS-P acts as an antagonist of TLR4 signalling by interfering with the functioning of LBP/CD14.
Lee
Sung-Hoon
SH
Department of Oromaxillofacial Infection and Immunity, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Kim
Kack-Kyun
KK
Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.|Department of Oromaxillofacial Infection and Immunity, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Rhyu
In-Chul
IC
Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.|Department of Periodontology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Koh
Sukhoon
S
Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Lee
Dae-Sil
DS
Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Choi
Bong-Kyu
BK
Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.|Department of Oromaxillofacial Infection and Immunity, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
D000954:Antigens, Surface; D002460:Cell Line; D005881:Gingiva / Q000382:microbiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics; D010636:Phenols / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors* / Q000502:physiology; D014208:Treponema / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000954:Antigens, Surface; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010636:Phenols; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D014867:Water; D018799:Intercellular Adhesion Molecule-1