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Enhanced release of IL‐1β and TNF‐α following endotoxin challenge from rat alveolar macrophages cultured in low‐Mg 2+ medium Volume 16, issue 2, June 2003

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Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, 1 ‐‐ 21‐24 Korimoto, Kagoshima 890‐0065, Japan

Our previous data have demonstrated that LPS‐stimulated alveolar macrophages produce higher levels of IL‐1β and TNF‐α 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‐1β and TNF‐α in low‐Mg 2+ medium than in normal‐Mg 2+ medium. The enhanced release of IL‐1β 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]‐κB and AP‐1). On the other hand, the enhanced release of TNF‐α 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‐κB inhibitor). From these results, we conclude that the enhanced release of IL‐1β and TNF‐α 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.