乌头酸脱羧酶1对BCG诱导巨噬细胞炎症反应的调控作用研究

doi:10.11843/j.issn.0366-6964.2024.04.031

Abstract

Abstract: Tuberculosis (TB) is a chronic respiratory disease caused by Mycobacterium tuberculosis (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 inducible protein associated with inflammation and infection, many studies have identified ACOD1 as one of the most upregulated genes under various conditions associated with infection. However, the role of ACOD1 in the regulation of RAW264.7 macrophage inflammatory response induced by attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection remains unclear. In this study, we investigated the effect of ACOD1 on RAW264.7 cell inflammatory response during BCG infection. In addition, we explored the role of ACOD1 in regulating BCG-induced RAW264.7 cell inflammatory response using small interfering RNAs targeting ACOD1. The experiment used Western blot, Quantitative Real-time PCR (qRT-PCR) and immunofluorescence to detect the levels of ACOD1, cytokines and TLR4/MyD88/NF-κB signaling pathway proteins. 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 activate 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.

Key words: aconitate decarboxylase 1, BCG, RAW264.7 cell, inflammatory response, TLR4/MyD88/NF-κB signaling pathway

CLC Number:

S852.618

DAI Fan, LIU Zhanyou, ZHANG Xuyang, LI Wu. Aconitate Decarboxylase 1 Could Regulate the Inflammatory Response Caused by BCG[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1696-1706.

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Aconitate Decarboxylase 1 Could Regulate the Inflammatory Response Caused by BCG

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