Lipopolysaccharides from Periodontopathic BacteriaPorphyromonas gingivalisandCapnocytophaga ochraceaAre 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-κB (NF-κB)-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, andFusobacterium nucleatum, and a non-oral bacterium,Escherichia coli, all species of the bacteria induced NF-κB-dependent CD25 expression in 7.7/huTLR2 cells. Although freeze-driedA.actinomycetemcomitans,F.nucleatum, andE.colialso induced CD25 expression in 7.7/huTLR4 cells, freeze-driedP.gingivalisdid not. Similarly, lipopolysaccharides (LPS) extracted fromA.actinomycetemcomitans,F.nucleatum, andE.coliinduced CD25 expression in 7.7/huTLR4 cells, but LPS fromP.gingivalisandC.ochraceadid not. Furthermore, LPS fromP.gingivalisandC.ochraceaattenuated CD25 expression in 7.7/huTLR4 cells induced by repurified LPS fromE.coli. LPS fromP.gingivalisandC.ochraceaalso inhibited the secretion of interleukin-6 (IL-6) from U373 cells, the secretion of IL-1β from human peripheral blood mononuclear cells, and ICAM-1 expression in human gingival fibroblasts induced by repurified LPS fromE.coli. These findings indicated that LPS fromP.gingivalisandC.ochraceaworked as antagonists for human TLR4. The antagonistic activity of LPS from these periodontopathic bacteria may be associated with the etiology of periodontal diseases.