title: Beryllium alters lipopolysaccharide-mediated intracellular phosphorylation and cytokine release in human peripheral blood mononuclear cells.
abstract: Beryllium exposure in susceptible individuals leads to the development of chronic beryllium disease, a lung disorder marked by release of inflammatory cytokine and granuloma formation. We have previously reported that beryllium induces an immune response even in blood mononuclear cells from healthy individuals. In this study, we investigate the effects of beryllium on lipopolysaccharide-mediated cytokine release in blood mononuclear and dendritic cells from healthy individuals. We found that in vitro treatment of beryllium sulfate inhibits the secretion of lipopolysaccharide-mediated interleukin 10, while the release of interleukin 1beta is enhanced. In addition, not all lipopolysaccharide-mediated responses are altered, as interleukin 6 release in unaffected upon beryllium treatment. Beryllium sulfate-treated cells show altered phosphotyrosine levels upon lipopolysaccharide stimulation. Significantly, beryllium inhibits the phosphorylation of signal transducer and activator of transducer 3, induced by lipopolysaccharide. Finally, inhibitors of phosphoinositide-3 kinase mimic the effects of beryllium in inhibition of interleukin 10 release, while they have no effect on interleukin 1beta secretion. This study strongly suggests that prior exposures to beryllium could alter host immune responses to bacterial infections in healthy individuals, by altering intracellular signaling.
authors.affiliation: Biosciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Silva
authors.forename: Kumkum
authors.initials: K
authors.lastname: Ganguly
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Fresquez
authors.forename: Goutam
authors.initials: G
authors.lastname: Gupta
authors.forename: T Mark
authors.initials: TM
authors.lastname: McCleskey
authors.forename: Anu
authors.initials: A
authors.lastname: Chaudhary
mesh_terms: D001608:Beryllium / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
chemical_list: D001608:Beryllium; D016207:Cytokines; D016753:Interleukin-10; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014443:Tyrosine; C508609:IL10 protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; C020711:beryllium sulfate