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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Surg+Res 2018 ; 221 (ä): 257-265 Nephropedia Template TP
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Effects of MgSO(4) on inhibiting Nod-like receptor protein 3 inflammasome involve decreasing intracellular calcium #MMPMID29229137
Chang YY; Kao MC; Lin JA; Chen TY; Cheng CF; Wong CS; Tzeng IS; Huang CJ
J Surg Res 2018[Jan]; 221 (ä): 257-265 PMID29229137show ga
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-1beta (IL-1beta) 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 (MgSO(4)), 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 mug/ml) plus nigericin (5 muM) (the LPS + Nig group) and LPS plus nigericin plus MgSO(4) (20 mM) [the LPS + Nig + M(20)] to facilitate investigations. Levels of IL-1beta, pyroptosis, and NLRP3 inflammasome induction as well as intracellular calcium were assayed. RESULTS: IL-1beta 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: MgSO(4) inhibits NLRP3 inflammasome, IL-1beta upregulation, and pyroptosis. The mechanism is consistent with decreased intracellular calcium levels.