title: Lipopolysaccharides from periodontopathic bacteria Porphyromonas gingivalis and Capnocytophaga ochracea are antagonists for human toll-like receptor 4.
abstract: Toll-like receptors (TLRs) 2 and 4 have recently been identified as possible signal transducers for various bacterial ligands. To investigate the roles of TLRs in the recognition of periodontopathic bacteria by the innate immune system, a Chinese hamster ovary (CHO) nuclear factor-kappaB (NF-kappaB)-dependent reporter cell line, 7.7, which is defective in both TLR2- and TLR4-dependent signaling pathways was transfected with human CD14 and TLRs. When the transfectants were exposed to freeze-dried periodontopathic bacteria, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Capnocytophaga ochracea, and Fusobacterium nucleatum, and a non-oral bacterium, Escherichia coli, all species of the bacteria induced NF-kappaB-dependent CD25 expression in 7.7/huTLR2 cells. Although freeze-dried A. actinomycetemcomitans, F. nucleatum, and E. coli also induced CD25 expression in 7.7/huTLR4 cells, freeze-dried P. gingivalis did not. Similarly, lipopolysaccharides (LPS) extracted from A. actinomycetemcomitans, F. nucleatum, and E. coli induced CD25 expression in 7.7/huTLR4 cells, but LPS from P. gingivalis and C. ochracea did not. Furthermore, LPS from P. gingivalis and C. ochracea attenuated CD25 expression in 7.7/huTLR4 cells induced by repurified LPS from E. coli. LPS from P. gingivalis and C. ochracea also inhibited the secretion of interleukin-6 (IL-6) from U373 cells, the secretion of IL-1beta from human peripheral blood mononuclear cells, and ICAM-1 expression in human gingival fibroblasts induced by repurified LPS from E. coli. These findings indicated that LPS from P. gingivalis and C. ochracea worked as antagonists for human TLR4. The antagonistic activity of LPS from these periodontopathic bacteria may be associated with the etiology of periodontal diseases.
authors.affiliation: Department of Periodontology, Nagasaki University School of Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. ayoshi@net.nagasaki-u.ac.jp
authors.forename: Atsutoshi
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kato
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hara
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002206:Capnocytophaga / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D029721:Drosophila Proteins; D004926:Escherichia coli / Q000378:metabolism; D005612:Freeze Drying; D016967:Fusobacterium nucleatum / Q000378:metabolism; D005881:Gingiva / Q000166:cytology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D010519:Periodontium; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D029721:Drosophila Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D018799:Intercellular Adhesion Molecule-1