Phosphoinositide 3-kinase β, phosphoinositide 3-kinase δ, and phosphoinositide 3-kinase γ mediate the anti-inflammatory effects of magnesium sulfate

Ping Ying Lee, Chen Hsien Yang, Ming Chang Kao, Nuan Yen Su, Pei Shan Tsai, Chun Jen Huang

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8 Citations (Scopus)

Abstract

Background We previously demonstrated that inhibiting phosphoinositide 3-kinase (PI3K) or activating L-type calcium channels blocked the anti-inflammatory effects of magnesium sulfate (MgSO4). However, the question as which class I PI3K isoform (PI3Kα, PI3Kβ, PI3Kδ, or PI3Kγ) is involved in this regard remains unstudied. The question as whether MgSO4 and L-type calcium channels interact to influence PI3K activation also remains unstudied. We therefore designed this study to test two hypotheses: (1) inhibiting PI3Kα, PI3Kβ, PI3Kδ, or PI3Kγ would block the anti-inflammatory effects of MgSO4 and (2) activating L-type calcium channels would block the effects of MgSO4 on activating PI3K. Materials and methods PI3K isoform investigation: macrophages (RAW264.7 cells) were treated with endotoxin, endotoxin plus MgSO4, or endotoxin plus MgSO4 plus the selective inhibitor of PI3Kα (PIK-75), PI3Kβ (TGX-221), PI3Kδ (IC-87114), or PI3Kγ (AS-252424). Calcium channel investigation: macrophages were treated with endotoxin, endotoxin plus MgSO4, or endotoxin plus MgSO4 plus the L-type calcium channel activator BAY-K8644. Results The endotoxin plus MgSO4 group presented lower concentrations of inflammatory mediators (macrophage inflammatory protein 2, tumor necrosis factor α, and interleukin 6, lower nuclear concentration of phosphorylated nuclear factor κB, lower cytosolic concentration of phosphorylated inhibitor κBα, and higher concentration of phosphorylated Akt (PI3K activation marker) than the endotoxin group (all P <0.05). These effects of MgSO4 were significantly reduced by TGX-221, IC-87114, or AS-252424, but not PIK-75. Additionally, BAY-K8644 blocked the effect of MgSO4 on activating PI3K. Conclusions MgSO4 exerts its anti-inflammatory effects through activating PI3Kβ, PI3Kδ, and PI3Kγ. The underlying mechanism appears to involve inhibition of L-type calcium channels.

Original languageEnglish
Pages (from-to)390-397
Number of pages8
JournalJournal of Surgical Research
Volume197
Issue number2
DOIs
Publication statusPublished - Aug 1 2015

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Keywords

  • Chemokine
  • Cytokine
  • Endotoxin
  • Macrophages
  • MgSO<inf>4</inf>
  • NF-κB

ASJC Scopus subject areas

  • Surgery

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