Tripartite-motif protein 21 knockdown extenuates LPS-triggered neurotoxicity by inhibiting microglial M1 polarization via suppressing NF-κB-mediated NLRP3 inflammasome activation.

Tripartite motif-containing 21 (TRIM21) has been confirmed to mediate the production of inflammatory mediators via NF-κB signaling. However, the function of TRIM21 in microglia-mediated neuroinflammation remains unclear. This study aimed to explore the effect of TRIM21 on LPS-activated BV2 microglia and its underlying mechanism. BV2 cells exposed to lipopolysaccharide (LPS) were used to simulated neuroinflammation in vitro. Loss-of-function and gain-of-function of TRIM21 in BV2 cells were used to assess the effect of TRIM21 on LPS-induced neuroinflammation. BV2 microglia and HT22 cells co-culture system were used to investigate whether TRIM21 regulated neuronal inflammation-mediated neuronal death. TRIM21 knockdown triggered the polarization of BV2 cells from M1 to M2 phenotype. Knockdown of TRIM21 reduced the secretion of TNF-α, IL-6, and IL-1β, while increased the content of IL-4 in LPS-treated cells. Knockdown of TRIM21 inhibited the expression of p65 and the binding activity of NF-κB-DNA. Additionally, TRIM21 siRNA eliminated the increase in NLRP3 and cleaved caspase-1 proteins expression and caspase-1 activity induced by LPS. TRIM21 knockdown could resist cytotoxicity induced by activated microglia, including increasing the viability of co-cultured HT22 cells and reducing the emancipation of LDH. Moreover, the increased apoptosis and caspase-3 activity of HT22 neurons induced by activated BV2 cells were blocked by TRIM21 siRNA. Blocking of NF-κB abolished the effect of TRIM21 in promoting the expression of M1 phenotype marker genes. Similarly, the blockade of NF-κB pathway eliminated the promotion of TRIM21 on neurotoxicity induced by neuroinflammation. TRIM21 knockdown suppressed the M1 phenotype polarization of microglia and neuroinflammation-mediated neuronal damage via NF-κB/NLRP3 inflammasome pathway, which suggested that TRIM21 might be a potential therapeutic target for the therapy of central nervous system diseases.

Xiao T ，Wan J ，Qu H ，Li Y ... -  《-》

Benzyl isothiocyanate inhibits inflammasome activation in E. coli LPS-stimulated BV2 cells.

Lee CM ，Lee DS ，Jung WK ，Yoo JS ，Yim MJ ，Choi YH ，Park S ，Seo SK ，Choi JS ，Lee YM ，Park WS ，Choi IW ... -  《-》

Carvedilol attenuates inflammatory reactions of lipopolysaccharide-stimulated BV2 cells and modulates M1/M2 polarization of microglia via regulating NLRP3, Notch, and PPAR-γ signaling pathways.

Khoshnavay Foumani M ，Amirshahrokhi K ，Namjoo Z ，Niapour A ... -  《-》

Targeting the NLRP3 Inflammasome-Related Pathways via Tianeptine Treatment-Suppressed Microglia Polarization to the M1 Phenotype in Lipopolysaccharide-Stimulated Cultures.

Ślusarczyk J ，Trojan E ，Głombik K ，Piotrowska A ，Budziszewska B ，Kubera M ，Popiołek-Barczyk K ，Lasoń W ，Mika J ，Basta-Kaim A ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia.

Huang MY ，Tu CE ，Wang SC ，Hung YL ，Su CC ，Fang SH ，Chen CS ，Liu PL ，Cheng WC ，Huang YW ，Li CY ... -  《BMC Complementary and Alternative Medicine》