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

4 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

Fingerprint

Inflammasomes
Calcium
Proteins
Interleukin-1
Nigericin
Caspase 1
Cell Size
Up-Regulation
Apoptosis
Multiprotein Complexes
Magnesium Sulfate
Calcium Signaling
Lipopolysaccharides
Leukemia
Cell Death

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

Effects of MgSO4 on inhibiting Nod-like receptor protein 3 inflammasome involve decreasing intracellular calcium. / Chang, Ya Ying; Kao, Ming Chang; Lin, Jui An; Chen, Tsung Ying; Cheng, Ching Feng; Wong, Chih Shung; Tzeng, I. Shiang; Huang, Chun Jen.

In: Journal of Surgical Research, Vol. 221, 01.01.2018, p. 257-265.

Research output: Contribution to journalArticle

Chang, Ya Ying ; Kao, Ming Chang ; Lin, Jui An ; Chen, Tsung Ying ; Cheng, Ching Feng ; Wong, Chih Shung ; Tzeng, I. Shiang ; Huang, Chun Jen. / Effects of MgSO4 on inhibiting Nod-like receptor protein 3 inflammasome involve decreasing intracellular calcium. In: Journal of Surgical Research. 2018 ; Vol. 221. pp. 257-265.
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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.",
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author = "Chang, {Ya Ying} and Kao, {Ming Chang} and Lin, {Jui An} and Chen, {Tsung Ying} and Cheng, {Ching Feng} and Wong, {Chih Shung} and Tzeng, {I. Shiang} and Huang, {Chun Jen}",
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T1 - Effects of MgSO4 on inhibiting Nod-like receptor protein 3 inflammasome involve decreasing intracellular calcium

AU - Chang, Ya Ying

AU - Kao, Ming Chang

AU - Lin, Jui An

AU - Chen, Tsung Ying

AU - Cheng, Ching Feng

AU - Wong, Chih Shung

AU - Tzeng, I. Shiang

AU - Huang, Chun Jen

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - ASC

KW - Caspase-1

KW - Magnesium sulfate

KW - Pyroptosis

KW - THP-1

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