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pmid12635866      Magnes+Res 2002 ; 15 (3-4): 153-60
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  • Mechanisms underlying the enhanced elevation of IL-1beta and TNF-alpha mRNA levels following endotoxin challenge in rat alveolar macrophages cultured with low-Mg2+ medium #MMPMID12635866
  • Oono H; Nakagawa M; Miyamoto A; Ishiguro S; Nishio A
  • Magnes Res 2002[Dec]; 15 (3-4): 153-60 PMID12635866show ga
  • We have previously shown that interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha mRNA levels in rat alveolar macrophages are increased in by endotoxin (lipopolysaccharide; LPS)- stimulation and further enhanced by culturing with low-Mg2+ medium. We have now investigated the mechanisms of underlying this enhancement by using some specific signal transduction inhibitors. The enhanced elevation of both mRNAs levels was suppressed by pretreatment with TMB-8 (which inhibits calcium release from the endoplasmic reticulum) or dexamethasone (which inhibits nuclear factor [NF]-kappaB and activator protein [AP]-1), but not with verapamil or nifedipine (which inhibits calcium channels). The enhancment of IL-1beta, but not TNF-alpha mRNA levels, was suppressed by pretreatment with W-7 (which inhibits calmodulin), whereas the enhancement of TNF-alpha mRNA levels was suppressed by pretreatment with U73122 (which inhibits phospholipase C). Curcumin (an inhibitor of AP-1), suppressed the increases in both mRNAs induced by low-Mg2+ medium alone, but had no suppressive effect on the levels of either mRNA after LPS-stimulation in low-Mg2+ medium. Pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB) prevented the elevation of TNF-alpha mRNA levels induced by low-Mg2+ medium without LPS-stimulation, but had no suppressive effect on IL-1beta mRNA levels. From these results, we conclude that the enhanced elevation of IL-1beta and TNF-alpha mRNA levels seen in LPS-stimulated alveolar macrophages in low-Mg2+ medium occurs partly via the same, and partly via different, signaling pathways.
  • |Animals[MESH]
  • |Calcium Signaling/drug effects[MESH]
  • |Cells, Cultured[MESH]
  • |DNA Primers[MESH]
  • |DNA, Complementary/biosynthesis/genetics[MESH]
  • |Endotoxins/*pharmacology[MESH]
  • |Interleukin-1/*biosynthesis[MESH]
  • |Lipopolysaccharides/pharmacology[MESH]
  • |Macrophages, Alveolar/drug effects/*metabolism[MESH]
  • |Magnesium Deficiency/*metabolism[MESH]
  • |RNA, Messenger/*biosynthesis[MESH]
  • |Rats[MESH]
  • |Signal Transduction/drug effects/physiology[MESH]
  • |Transcription, Genetic/drug effects[MESH]


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