69 Citations (Scopus)

Abstract

BackgroundMagnesium sulphate (MgSO4) has potent anti-inflammatory capacity. It is a natural calcium antagonist and a potent L-type calcium channel inhibitor. We sought to elucidate the possible role of calcium, the L-type calcium channels, or both in mediating the anti-inflammatory effects of MgSO4.MethodsRAW264.7 cells, an immortalized murine macrophage-like cell line, were treated with phosphate buffered saline, MgSO4, lipopolysaccharide (LPS), LPS plus MgSO4, LPS plus MgSO4 plus extra-cellular supplement with calcium chloride (CaCl 2), or LPS plus MgSO4 plus the L-type calcium channel activator BAY-K8644. After harvesting, the production of inflammatory molecules was evaluated. Because the production of endotoxin-induced inflammatory molecules is regulated by the crucial transcription factor nuclear factor (NF)-κB, we also evaluated the expression of NF-B.ResultsLPS significantly induced the production of inflammatory molecules, including macrophage inflammatory protein-2, tumour necrosis factor-, interleukin (IL)-1, IL-6, nitric oxide/inducible nitric oxide synthase, and prostaglandin E2/cyclo-oxygenase-2. LPS also induced NF-B activation, as inhibitor-B degradation, NF-B nuclear translocation, and NF-κB-DNA binding activity were significantly increased in LPS-treated RAW264.7 cells. MgSO4, in contrast, significantly inhibited the LPS-induced inflammatory molecules production and NF-κB activation. Moreover, the effects of MgSO4 on inflammatory molecules and NF-κB werereversed by extra-cellular calcium supplement with CaCl2 and L-type calcium channel activator BAY-K8644.ConclusionsMgSO4 significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-κB activation in activated RAW264.7 cells. The effects of MgSO4 on inflammatory molecules and NF-κB may involve antagonizing calcium, inhibiting the L-type calcium channels, or both.

Original languageEnglish
Pages (from-to)44-51
Number of pages8
JournalBritish Journal of Anaesthesia
Volume104
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • Enzymes, cyclo-oxygenase
  • Intensive care
  • Ions, ion channels, voltage-gated
  • Ions, magnesium
  • Nitric oxide

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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