title: TLR4 is a target of environmentally relevant concentration of lead.
abstract: 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 5μg/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(-) baseline, IL-1β 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(-) production, and decrease IL-6 and TNF-α secretion; in macrophages stimulated with LPS from S. typhimurium, Pb decreased proliferation after 36h, induced a biphasic effect on NO(-) production, and enhance the secretion of IL-1β, IL-6 and TNF-α. Results suggest that TLR4 is a target for the Pb effect, which up to 5.0μg/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.
authors.affiliation: Departamento de Toxicología, Cinvestav, IPN, Mexico, D.F., Mexico.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Luna
authors.forename: Leonor C
authors.initials: LC
authors.lastname: Acosta-Saavedra
authors.forename: Marcela
authors.initials: M
authors.lastname: Martínez
authors.forename: Nallely
authors.initials: N
authors.lastname: Torres-Avilés
authors.forename: Rocío
authors.initials: R
authors.lastname: Gómez
authors.forename: Emma S
authors.initials: ES
authors.lastname: Calderón-Aranda
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D004926:Escherichia coli / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D004785:Environmental Pollutants; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C008261:lead acetate