Probucol Inhibits The Secretion Of IL-1? And IL-18 By Down-regulating NLRP3 Inflammasome Expression In THP-1 Macrophages

Objective: This study aimd to explore the association between the suppressed secretion of IL-1? and IL-18 mediated by probucol and the down-regulation of NLRP3 or NLRP1 in THP-1 marcophages.Methods: The cultured THP-1 mononuclear cells were selected as the experimental subjects.Then with the treatment of PMA the THP-1 cells differentiated to the macrophages.By giving three different kinds of treatments,the cells were divided by three groups: the blank control group,the LPS group,and the probucol group.The level of IL-18 and IL-1? were detected by the ELISA.The qPCR was used to detected the transcription of the gene of ASC,Caspase-1 and NLRP3 or NLRP1.Results: The IL-1? secreted by the THP-1 macrophages in the LPS group was significantly higher than that of blank control group(31.39 ± 2.49 vs 4.07 ± 0.22,p<0.01).While in the probucol group,the levels of IL-1? was significantly suppressed(5.86 ± 0.41 vs 31.39 ± 2.49,p<0.01).As for the level of IL-18,THP-1macrophages in the LPS group secreted significantly higher levels of IL-18 than that of the blank control group(36.00 ± 1.50 vs 21.45 ± 0.48,p<0.01).The level of IL-18 in the probucol group was significantly supressed(24.15 ± 1.31 vs 36.00 ± 1.50,p<0.01).Besides,the mRNA levels of ASC,Caspase-1 and NLRP3 and NLRP1 were also detected.The LPS group showed higher levels of ASC mRNA compared to the control group(1.43 ± 0.04 vs 1.00 ± 0.06,p<0.01).While,the probucol group exhibited lower levels of ASC gene transcription compared with LPS group(0.95 ± 0.01 vs1.43 ± 0.04,p<0.01).As for the gene transcription of Caspase-1,the same trend was also observed in the LPS group compared to the control group(1.20 ± 0.02 vs 1.00 ± 0.01,p<0.01).The probucol group exhibited lower levels of Caspase-1 gene transcription compared with the LPS group(0.30 ± 0.01 vs 1.20 ± 0.02,p<0.01).The LPS group showed significantly higher levels of gene transcription in NLRP3 compared to the control group(1.38 ± 0.02 vs 1.00 ± 0.01,p<0.01).The probucol group showed significantly lower level of gene transcription in NLRP3(0.42 ± 0.01 vs 1.38 ± 0.02,p<0.01).Although the mRNA level of NLRP1 in LPS groups was greater than that of the control group(1.43 ± 0.07 vs 1.00 ±0.04,p<0.01),the trend in probucol group showed no statistic significance compared with the LPS group(1.43 ± 0.07 vs1.35 ± 0.13,p>0.05).Conclusion: The Probucol can perform its anti-inflammation effect by suppressing the secretion of IL-18 and IL-1? via the down-regulation of NLRP3 inflammasome expression in THP-1 macrophages.