Lipoteichoic acid acts as an antagonist and an agonist of lipopolysaccharide on human gingival fibroblasts and monocytes in a CD14-dependent manner

CD14 has been implicated as a receptor of lipoteichoic acid (LTA) and other bacterial components as well as lipopolysaccharide (LPS), Since the struct ures of LTAs from various gram-positive bacteria are heterogeneous, we anal yzed the effects of LTAs on the secretion of interleukin-8 (IL-8) by high- and low-CD14-expressing (CD14(high) and CD14(low)) human gingival fibroblas ts (HGF). While Bacillus subtilis LTA had an IL-8-inducing effect on CD14(h igh) HGF which was considerably weaker than that of LPS, Streptococcus sang uis and Streptococcus mutans LTAs had practically no effect on the cells. B . subtilis LTA had only a weak effect on CD14(low) HGF, as did LPS. S. sang uis and S. mutans LTAs at a 1,000-fold excess each completely inhibited the IL-8-inducing activities of both LPS and a synthetic lipid A on CD14(high) HGF, The effect of LPS was also inhibited by the presence of an LPS antago nist, synthetic lipid A precursor IVA (LA-14-PP), with a 100-fold higher po tency than S. sanguis and S. mutans LTAs and by anti-CD14 monoclonal antibo dy (MAb). S. sanguis and S. mutans LTAs, LA-14-PP, and anti-CD14 MAb had no significant effect on phorbol myristate acetate-stimulated IL-8 secretion by HGF. These LTAs also inhibited the IL-8-inducing activity of B. subtilis LTA on CD14(high) HGF, as did LA-14-PP and anti-CD14 MAb, The antagonistic and agonistic functions of LTAs were also observed with human monocytes. B inding of fluorolabeled LPS to human monocytes was inhibited by S. sanguis LTA, although the inhibition was 100 times weaker than that of LPS itself, and anti-CD14 MAb inhibited fluorolabeled LPS and S. sanguis LTA binding. B inding of LTAs to CD14 was also observed with nondenaturing polyacrylamide gel electrophoresis, These results indicate that LTAs act as antagonists or agonists via a CD14-dependent mechanism, probably due to the heterogeneous structure of LTAs, and that an antagonistic LTA might be a useful agent fo r suppressing the periodontal disease caused by gram-negative bacteria.