Effects of MgSO4 on inhibiting Nod-like receptor protein 3 inflammasome involve decreasing intracellular calcium

Ya Ying Chang, Ming Chang Kao, Jui An Lin, Tsung Ying Chen, Ching Feng Cheng, Chih Shung Wong, I. Shiang Tzeng, Chun Jen Huang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background Nod-like receptor protein 3 (NLRP3) inflammasome is a multiprotein complex composed of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain. Activation of NLRP3 inflammasome leads to interleukin-1β (IL-1β) upregulation and pyroptosis, a proinflammatory cell death characterized by increased cell size. Of note, calcium signaling is crucial for NLRP3 inflammasome activation. This study elucidated the effects of magnesium sulfate (MgSO4), a potent calcium antagonist, on modulating NLRP3 inflammasome. Materials and methods THP-1 cells, the human monocytic leukemia cell line, were treated with lipopolysaccharide (LPS, 1 μg/ml) plus nigericin (5 μM) (the LPS + Nig group) and LPS plus nigericin plus MgSO4 (20 mM) [the LPS + Nig + M(20)] to facilitate investigations. Levels of IL-1β, pyroptosis, and NLRP3 inflammasome induction as well as intracellular calcium were assayed. Results IL-1β concentration of the LPS + Nig + M(20) group was significantly lower than the LPS + Nig group (P = 0.001). Cell size of the LPS + Nig + M(20) group was significantly smaller than the LPS + Nig group (P < 0.001). Level of pyroptotic cell death of the LPS + Nig + M(20) group was significantly lower than the LPS + Nig group (P = 0.004). NLRP3 mRNA and protein concentrations of the LPS + Nig + M(20) group were also significantly lower than the LPS + Nig group (P = 0.021 and P < 0.001). Similarly, apoptosis-associated speck-like protein containing a caspase recruitment domain speck formation ratio and caspase-1 concentration of the LPS + Nig + M(20) group were significantly lower than the LPS + Nig group (both P < 0.001). The change in intracellular calcium level of the LPS + Nig + M(20) group was significantly smaller than the LPS + Nig group (P = 0.001). Conclusions MgSO4 inhibits NLRP3 inflammasome, IL-1β upregulation, and pyroptosis. The mechanism is consistent with decreased intracellular calcium levels.

Original languageEnglish
Pages (from-to)257-265
Number of pages9
JournalJournal of Surgical Research
Volume221
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • ASC
  • Caspase-1
  • Magnesium sulfate
  • Pyroptosis
  • THP-1

ASJC Scopus subject areas

  • Surgery

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