Effects of MgSO4 on inhibiting Nod-like receptor protein 3 inflammasome involve decreasing intracellular calcium.
J Surg Res
; 221: 257-265, 2018 01.
Article
em En
| MEDLINE
| ID: mdl-29229137
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-1ß (IL-1ß) 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 ANDMETHODS:
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-1ß, pyroptosis, and NLRP3 inflammasome induction as well as intracellular calcium were assayed.RESULTS:
IL-1ß 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-1ß upregulation, and pyroptosis. The mechanism is consistent with decreased intracellular calcium levels.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinalização do Cálcio
/
Inflamassomos
/
Piroptose
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Proteína 3 que Contém Domínio de Pirina da Família NLR
/
Sulfato de Magnésio
Limite:
Humans
Idioma:
En
Revista:
J Surg Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Taiwan