AlCl3 inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production through suppressing NF-κB signaling pathway in murine peritoneal macrophages

Aluminum (Al), a common environmental pollutant, has been reported to inhibit the immune functions of macrophage. However, the mechanisms involved remain unclear. In this study, murine peritoneal macrophages were exposed to 0, 0.27, 0.54, and 1.08 mg/mL of aluminium chloride (AlCl₃) for 24 h, and then treated with 1 μg/mL lipopolysaccharide (LPS) for another 6 h. No addition of both AlCl₃ and LPS serviced as control group. We observed that AlCl₃ has cytotoxicity in murine peritoneal macrophages, showing a decrease in cell viability and an increase in lactate dehydrogenase release. Besides, AlCl₃ exposure restrained the LPS-induced NLR pyrin domain containing 3 (NLRP3) inflammasome activation presented as NLRP3 expressions reduction, caspase-1 cleavage inhibition and interleukin 1 beta (IL-1β) maturation lessened. Meanwhile, AlCl₃ exposure decreased LPS-induced IKKβ activity, IκBα phosphorylation, the phosphorylation and mRNA expression of NF-κB p65, as well the genes expression and concentration in medium supernatant of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). The results suggested that AlCl₃ inhibited the activation of NF-κB signaling pathway induced by LPS, which maybe one of the upstream signals involved in the inhibition of NLRP3 inflammasome activation by AlCl₃. This research can provide theoretical basis for understanding the immune toxicity of Al, and deepening the cognition of Al exposure hazards to immune response.

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