Magnesium Sulfate Inhibits Activator Protein-1 Upregulation in Endotoxin-activated Murine Macrophages

ObjectiveThe expression of inflammatory molecules is regulated by the transcription factor activator protein-1 (AP-1), a heterodimeric protein that consists of proteins from various families, including c-Jun and c-Fos. We sought to elucidate whether MgSO4 regulates the activation of AP-1 in endotoxin-activated RAW264.7 cells, a murine macrophage-like cell line. The possible roles of the L-type calcium channels in this process were also elucidated.Materials and MethodsRAW264.7 cells were treated with phosphate buffered saline, MgSO4, lipopolysaccharide (LPS), LPS plus MgSO4 (20 mM), or LPS plus MgSO4 plus the L-type calcium channel activator BAY-K8644 (1 μM). After harvesting, expression of AP-1 was evaluated.ResultsLPS induced AP-1 activation based on the fact that the nuclear protein concentrations of AP-1 components, including c-Jun and c-Fos, as well as the AP-1 DNA-binding activity, were significantly increased in LPS-treated RAW264.7 cells. MgSO4, in contrast, significantly inhibited LPS-induced AP-1 activation in activated RAW264.7 cells. Moreover, the effect of MgSO4 on AP-1 was reversed by BAY-K8644.ConclusionMgSO4 inhibited AP-1 activation in LPS-treated macrophages and the mechanism may involve the L-type calcium channels.