title: Osmotic regulation of cytokine synthesis in vitro.
abstract: These studies were undertaken to investigate the therapeutic mechanism of saturated solutions of KI, used to treat infectious and inflammatory diseases. The addition of 12-50 mM KI to cultured human peripheral blood mononuclear cells resulted in 319-395 mosM final solute concentration and induced interleukin (IL)-8 synthesis. Maximal IL-8 production was seen when 40 mM salt was added (375 mosM) and was equal to IL-8 induced by endotoxin or IL-1 alpha. However, there was no induction of IL-1 alpha, IL-1 beta, or tumor necrosis factor to account for the synthesis of IL-8; the effect of KI was not due to contaminating endotoxins. Hyperosmolar NaCl also induced IL-8 and increased steady-state levels of IL-8 mRNA similar to those induced by IL-1 alpha. IL-8 gene expression was elevated for 96 hr in peripheral blood mononuclear cells incubated with hyperosmolar NaCl. In human THP-1 macrophagic cells, osmotic stimulation with KI, NaI, or NaCl also induced IL-8 production. IL-1 signal transduction includes the phosphorylation of the p38 mitogen-activated protein kinase that is observed following osmotic stress. Using specific blockade of this kinase, a dose-response inhibition of hyperosmolar NaCl-induced IL-8 synthesis was observed, similar to that in cells stimulated with IL-1. Thus, these studies suggest that IL-1 and osmotic shock utilize the same mitogen-activated protein kinase for signal transduction and IL-8 synthesis.
authors.affiliation: Department of Medicine, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Shapiro
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000097:blood; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D016133:Polymerase Chain Reaction; D011193:Potassium Iodide / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007375:Interleukin-1; D016209:Interleukin-8; D011725:Pyridines; D012333:RNA, Messenger; D011193:Potassium Iodide; D012965:Sodium Chloride; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093642:SB 203580