title: Calcium mobilizing treatment acts as a co-signal for TLR-mediated induction of Interleukin-12 (IL-12p70) secretion by murine bone marrow-derived dendritic cells.
abstract: We sought to determine whether pharmacological calcium-mobilizing agents could act in cooperation with Toll-like receptor (TLR) signals to induce high-level IL-12 production from murine bone marrow-derived dendritic cells. We found that calcium mobilization alone induced no IL-12, yet dramatically enhanced IL-12p70 secretion elicited by TLR ligands. Enhanced IL-12 production induced by calcium ionophore plus single TLR ligands, but not through dual TLR ligands, was inhibited by the calcineurin antagonist cyclosporine A, suggesting divergent mechanisms of IL-12 induction. Dendritic cells activated with calciumionophore plus the TLR9 ligand ODN1826 could induce Th1 polarization in naïve murine CD4posT cells at levels equal or superior to dendritic cells activated with the most efficient TLR ligand pairing; ODN1826 plus bacterial lipopolysaccharide. Parallel analysis of 38 inflammation-associated soluble products showed calciumionophore enhancement was restricted to a small set of factors. These data demonstrate previously undocumented activation co-signals for IL-12 production by dendritic cells.
authors.affiliation: Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Huang
authors.affiliation: Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, United States.
authors.forename: Loral
authors.initials: L
authors.lastname: Showalter
authors.affiliation: Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, United States.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, United States.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Czernliecki
authors.affiliation: Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, United States. Electronic address: dendritic_cell@hotmail.com.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Koski
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D019703:Calcineurin / Q000378:metabolism; D061207:Calcium Ionophores / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D061207:Calcium Ionophores; C423449:CpG ODN 1826; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; D016572:Cyclosporine; D019703:Calcineurin
keywords: Calcium mobilization; Dentritic cell; IL-12; Th polarization; Toll-like receptor