JOURNAL ARTICLE

L-type calcium channels are involved in mediating the anti-inflammatory effects of magnesium sulphate

C Y Lin, P S Tsai, Y C Hung, C J Huang
British Journal of Anaesthesia 2010, 104 (1): 44-51
19933511

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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