title: L-type calcium channels are involved in mediating the anti-inflammatory effects of magnesium sulphate.
abstract: BACKGROUND
  Magnesium sulphate (MgSO(4)) 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 MgSO(4).
  
  
  METHODS
  RAW264.7 cells, an immortalized murine macrophage-like cell line, were treated with phosphate buffered saline, MgSO(4), lipopolysaccharide (LPS), LPS plus MgSO(4), LPS plus MgSO(4) plus extra-cellular supplement with calcium chloride (CaCl(2)), or LPS plus MgSO(4) 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)-kappaB, we also evaluated the expression of NF-kappaB.
  
  
  RESULTS
  LPS significantly induced the production of inflammatory molecules, including macrophage inflammatory protein-2, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, nitric oxide/inducible nitric oxide synthase, and prostaglandin E(2)/cyclo-oxygenase-2. LPS also induced NF-kappaB activation, as inhibitor-kappaB degradation, NF-kappaB nuclear translocation, and NF-kappaB-DNA binding activity were significantly increased in LPS-treated RAW264.7 cells. MgSO(4), in contrast, significantly inhibited the LPS-induced inflammatory molecules production and NF-kappaB activation. Moreover, the effects of MgSO(4) on inflammatory molecules and NF-kappaB were reversed by extra-cellular calcium supplement with CaCl(2) and L-type calcium channel activator BAY-K8644.
  
  
  CONCLUSIONS
  MgSO(4) significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-kappaB activation in activated RAW264.7 cells. The effects of MgSO(4) on inflammatory molecules and NF-kappaB may involve antagonizing calcium, inhibiting the L-type calcium channels, or both.
authors.affiliation: Department of Anaesthesiology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Lin
authors.forename: P S
authors.initials: PS
authors.lastname: Tsai
authors.forename: Y C
authors.initials: YC
authors.lastname: Hung
authors.forename: C J
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002461:Cell Line, Transformed; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008278:Magnesium Sulfate / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D008278:Magnesium Sulfate