TLR4 is a target of environmentally relevant concentration of lead.

Lead (Pb) alters the susceptibility to different pathogens suggesting that macrophage-mediated defense mechanisms, through activation of toll-like receptors (TLRs), may be affected by Pb. The aim of this study was to test whether activation of TLR4 is a targeted molecule to the effect of environmentally relevant Pb concentrations (0.05, 0.5 and 5 mu g/dL). The function of macrophages activated through TLR4 was evaluated using as TLR4 ligand lipopolysaccharides (LPSs) from two different pathogens: Escherichia coli and Salmonella typhimurium. Pb induced proliferation, increased the NO center dot- baseline, IL-1 beta and IL-6 secretion. Interestingly, Pb exposure induced differential effects on cells stimulated with the two LPS used: in macrophages stimulated with LPS from E. coli, Pb caused an early decrease in proliferation, increase NO center dot- production, and decrease IL-6 and TNF-alpha secretion; in macrophages stimulated with LPS from S. typhimurium, Pb decreased proliferation after 36 h, induced a biphasic effect on NO center dot- production, and enhance the secretion of IL-1 beta, IL-6 and TNF-alpha. Results suggest that TLR4 is a target for the Pb effect, which up to 5.0 mu g/dL affect immune competence against pathogens, dependent on the bacterial species. This effect may be attributable to structural differences that determine LPS affinity for TLR4. (C) 2012 Elsevier Ireland Ltd. All rights reserved.