title: Enhanced release of IL-1beta and TNF-alpha following endotoxin challenge from rat alveolar macrophages cultured in low-mg(2+) medium.
abstract: Our previous data have demonstrated that LPS-stimulated alveolar macrophages produce higher levels of IL-1beta and TNF-alpha mRNA in low-Mg(2+) medium than in normal-Mg(2+) medium. In this study, we examined whether the increased mRNA levels are correlated with the release of both cytokines. LPS-stimulated alveolar macrophages released higher amounts of IL-1beta and TNF-alpha in low-Mg(2+) medium than in normal-Mg(2+) medium. The enhanced release of IL-1beta was completely suppressed by pretreatment with verapamil (a calcium entry blocker), U73122 (a phospholipase C inhibitor), W-7 (a calmodulin inhibitor), and curcumin (an activator-protein [AP]-1 inhibitor), and weakly suppressed by dexamethasone (which inhibits nuclear factor [NF]-kappaB and AP-1). On the other hand, the enhanced release of TNF-alpha was completely suppressed by U73122, and strongly suppressed by TMB-8 (which inhibits calcium release from the endoplasmic reticulum) and W-7, and weakly suppressed by pyrrolidine dithiocarbamate (a NF-kappaB inhibitor). From these results, we conclude that the enhanced release of IL-1beta and TNF-alpha from LPS-stimulated alveolar macrophages in low-Mg(2+) medium depends partly on the enhanced synthesis of both cytokines, and occurs partly via identical, and partly via different, signaling pathways.
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, 1 - 21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Shogi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ishiguro
authors.forename: Akira
authors.initials: A
authors.lastname: Nishio
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000893:Anti-Inflammatory Agents; D002121:Calcium Channel Blockers; D004731:Endotoxins; D004791:Enzyme Inhibitors; D004963:Estrenes; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D012333:RNA, Messenger; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C017967:W 7; D003907:Dexamethasone; D008274:Magnesium; D003474:Curcumin; D002118:Calcium