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

Cay-Huyen Chen a, b, Pei-Shan Tsai c, Chun-Jen Huang a, b

aDepartment of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan
bSchool of Medicine, Tzu Chi University, Hualien, Taiwan
cCollege of Nursing, Taipei Medical University, Taipei, Taiwan

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Abstract

Objective
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 μM). 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.


Keywords

AP-1; LPS; L-type calcium channels; MgSO4


 

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