Article ; Online: L-type calcium channels are involved in mediating the anti-inflammatory effects of magnesium sulphate.
British journal of anaesthesia
2010 Volume 104, Issue 1, Page(s) 44–51
Abstract: ... of calcium, the L-type calcium channels, or both in mediating the anti-inflammatory effects of MgSO(4 ... NF-kappaB may involve antagonizing calcium, inhibiting the L-type calcium channels, or both. ... Background: Magnesium sulphate (MgSO(4)) has potent anti-inflammatory capacity. It is a natural ...
| 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. |
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| MeSH term(s) | Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/drug effects ; Cell Line, Transformed ; Inflammation Mediators/metabolism ; Lipopolysaccharides/pharmacology ; Macrophages/drug effects ; Macrophages/metabolism ; Magnesium Sulfate/pharmacology ; Mice ; NF-kappa B/metabolism ; RNA, Messenger/genetics ; Up-Regulation/drug effects | |||||
| Chemical Substances | Anti-Inflammatory Agents, Non-Steroidal ; Calcium Channel Blockers ; Calcium Channels, L-Type ; Inflammation Mediators ; Lipopolysaccharides ; NF-kappa B ; RNA, Messenger ; Magnesium Sulfate (7487-88-9) | |||||
| Language | English | |||||
| Publishing date | 2010-01 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 80074-0 | |||||
| ISSN | 1471-6771 ; 0007-0912 | |||||
| ISSN (online) | 1471-6771 | |||||
| ISSN | 0007-0912 | |||||
| DOI | 10.1093/bja/aep336 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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