Distinct responses between healthy and cirrhotic human livers upon LPS challenge: possible implications for ACLF.
Distinct responses between healthy and cirrhotic human livers upon LPS challenge: possible implications for ACLF.
复制标题
健康和肝硬化人类肝脏对 LPS 挑战的不同反应：对 ACLF 的可能影响。
DOI：
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
P. Olinga
中科院分区：
文献类型：
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作者：
S. Suriguga;Mei Li;Theerut Luangmonkong;M. Boersema;K. D. de Jong;D. Oosterhuis;A. Gorter;L. Beljaars;P. Olinga
背景与目的
BACKGROUND & AIMS
Patients with acute-on-chronic liver failure (ACLF) are at risk of developing acute hepatic decompensation and organ failures with an unraveled complex mechanism. An altered immune response towards insults in cirrhotic compared to healthy livers may contribute to the ACLF development. Therefore, we aim to investigate the differences in inflammatory responses between cirrhotic and healthy livers using human precision-cut liver slices (PCLS) upon LPS challenge.
METHODS
PCLS prepared from livers of cirrhotic patients or healthy donors of liver transplantation were incubated ex-vivo with or without lipopolysaccharide (LPS) up to 48 h. Viability test, qRT-PCR and multiplex cytokine assay were performed.
RESULTS
Regulation of the LPS receptors during incubation or with LPS challenge differed between healthy versus cirrhotic PCLS. LPS upregulated TLR-2 in healthy PCLS solely (p<0.01). Culturing for 48h induced a stronger inflammatory response in the cirrhotic than healthy PCLS. Upon LPS stimulation, cirrhotic PCLS secreted more pro-inflammatory cytokines (IL-8, IL-6, TNF-α, eotaxin and VEGF) significantly and less anti-inflammatory cytokine (IL-1ra) than those of healthy.
CONCLUSIONS
To sum, cirrhotic PCLS released more pro-inflammatory and less anti-inflammatory cytokines after LPS stimuli than healthy, leading to dysregulated inflammatory response. These events could possibly resemble the liver immune response in ACLF.
影响因子：
3.7
作者：
Zimmermann HW;Seidler S;Gassler N;Nattermann J;Luedde T;Trautwein C;Tacke F
通讯作者：
Tacke F