Chemical inhibition of TRAF6-TAK1 axis as therapeutic strategy of endotoxin-induced liver disease

Kim, Song Hee; Baek, Seungil; Jung, Ji‐Hye; Lee, Eung-Seok; Na, Younghwa; Hwang, Bang Yeon; Roh, Yoon-Seok; Hong, Jin Tae; Han, Sang‐Bae; Kim, Youngsoo

doi:10.1016/j.biopha.2022.113688

Cited by 5 publications

(2 citation statements)

References 42 publications

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“…The cells were serum-starved for 12 h before treatment, and the control group was treated with vehicle correspondence. To induce inflammation in macrophages, the cells were treated with 0.1 µg/mL LPS, as previously reported [43][44][45]. Moreover, LPS (0.1 µg/mL)/ATP (5 mM) was adopted to induce inflammasome in macrophages, as previously reported [46].…”

Section: Cell Culturementioning

confidence: 97%

Castanopsis sieboldii Extract Alleviates Acute Liver Injury by Antagonizing Inflammasome-Mediated Pyroptosis

Kim

Cho

Kang

et al. 2023

IJMS

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Castanopsis sieboldii (CS), a subtropical species, was reported to have antioxidant and antibacterial effects. However, the anti-inflammatory effects of CS have not been studied. This study aimed to investigate whether the 70% ethanol extract of the CS leaf (CSL3) inhibited lipopolysaccharide (LPS)-induced inflammatory responses and LPS and ATP-induced pyroptosis in macrophages. CSL3 treatment inhibited NO release and iNOS expression in LPS-stimulated cells. CSL3 antagonized NF-κB and AP-1 activation, which was due to MAPK (p38, ERK, and JNK) inhibition. CSL3 successfully decreased NLRP3 inflammasome activation and increased IL-1β expression. CSL3 treatment diminished LPS and ATP-induced pore formation in GSDMD. The in vivo effect of CSL3 on acute liver injury was evaluated in a CCl4-treated mouse model. CCl4 treatment increased the activity of serum alanine aminotransferase and aspartate aminotransferase, which decreased by CSL3. In addition, CCl4-induced an increase in TNF-α, and IL-6 levels decreased by CSL3 treatment. Furthermore, we verified that the CCl4-induced inflammasome and pyroptosis-related gene expression in liver tissue and release of IL-1β into serum were suppressed by CSL3 treatment. Our results suggest that CSL3 protects against acute liver injury by inhibiting inflammasome formation and pyroptosis.

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Section: Cell Culturementioning

confidence: 97%

Castanopsis sieboldii Extract Alleviates Acute Liver Injury by Antagonizing Inflammasome-Mediated Pyroptosis

Kim

Cho

Kang

et al. 2023

IJMS

View full text Add to dashboard Cite

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“…GSDMD-deficient mice showed significantly increased expression of Lps-binding protein, which is known to be an indicator of LPS exposure, and upregulated expression of TLR4 and CD14 ( 97 ). Owing to increased intestinal permeability, bacterial LPS can be carried to the liver via the portal vein, wherein it can bind to TLR4 on the surface of hepatic Kupffer cells and trigger an immunological response in the liver ( 98 ). The mechanism may be related to the fact that GSDMD knockdown inhibits pyroptosis but promotes apoptosis, indicating the tampering effect of GSDMD between different types of cell death ( 99 ).…”

Section: Inflammasomes and Pyroptosis In Aildsmentioning

confidence: 99%

Inflammasome and pyroptosis in autoimmune liver diseases

et al. 2023

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Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and IgG4-related sclerosing cholangitis (IgG4-SC) are the four main forms of autoimmune liver diseases (AILDs), which are all defined by an aberrant immune system attack on the liver. Most previous studies have shown that apoptosis and necrosis are the two major modes of hepatocyte death in AILDs. Recent studies have reported that inflammasome-mediated pyroptosis is critical for the inflammatory response and severity of liver injury in AILDs. This review summarizes our present understanding of inflammasome activation and function, as well as the connections among inflammasomes, pyroptosis, and AILDs, thus highlighting the shared features across the four disease models and gaps in our knowledge. In addition, we summarize the correlation among NLRP3 inflammasome activation in the liver-gut axis, liver injury, and intestinal barrier disruption in PBC and PSC. We summarize the differences in microbial and metabolic characteristics between PSC and IgG4-SC, and highlight the uniqueness of IgG4-SC. We explore the different roles of NLRP3 in acute and chronic cholestatic liver injury, as well as the complex and controversial crosstalk between various types of cell death in AILDs. We also discuss the most up-to-date developments in inflammasome- and pyroptosis-targeted medicines for autoimmune liver disorders.

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