Aconitate Decarboxylase 1 Could Regulate the Inflammatory Response Caused by BCG
Tuberculosis(TB)is a chronic respiratory disease caused by Mycobacterium tuberculo-sis(Mtb).There is mounting evidence that inflammatory response plays an important role in regulating the host immune responses.Aconitate decarboxylase 1(ACOD1)is a stress-related in-ducible protein associated with inflammation and infection,many studies have identified ACOD1 as one of the most upregulated genes under various conditions associated with infection.Howev-er,the role of ACOD1 in the regulation of RAW264.7 macrophage inflammatory response in-duced by attenuated Mycobacterium bovis Bacillus Calmette-Guérin(BCG)infection remains un-clear.In this study,we investigated the effect of ACOD1 on RAW264.7 cell inflammatory re-sponse during BCG infection.In addition,we explored the role of ACOD1 in regulating BCG-in-duced RAW264.7 cell inflammatory response using small interfering RNAs targeting ACOD1.The experiment used Western blot,Quantitative Real-time PCR(qRT-PCR)and immunofluores-cence to detect the levels of ACOD1,cytokines and TLR4/MyD88/NF-KB signaling pathway pro-teins.The results demonstrated that BCG could induce macrophage inflammatory response and ACOD1 upregulation in a time and concentration-dependent manner;Knockdown of ACOD1 could attenuate BCG-induced inflammatory response in RAW264.7 cells.Moreover,we found that ACOD1 knockdown decreased the expression of IL-1β,TNF-α,IL-6,COX2,iNOS,and increased the levels of anti-inflammatory cytokines about IL-4 and IL-10;ACOD1 can also acti-vate TLR4/MyD88/NF-κB signaling pathway,decreased the levels of TLR4,MyD88,TRAF6,p-NF-κB p65.These results indicated that ACOD1 could regulate inflammatory response caused by BCG through TLR4/MyD88/NF-κB signaling pathway.
万方数据
维普
