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

Objectives: The 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 Methods: RAW264.7 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 mu M). After harvesting, expression of AP-1 was evaluated. Results: LPS 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. Conclusion: MgSO4 inhibited AP-1 activation in LPS-treated macrophages and the mechanism may involve the L-type calcium channels.