Distinct responses between healthy and cirrhotic human livers upon lipopolysaccharide challenge: Possible implications for acute-on-chronic liver failure
Issued Date
2022-08-01
Resource Type
ISSN
01931857
eISSN
15221547
Scopus ID
2-s2.0-85134854493
Pubmed ID
35727919
Journal Title
American Journal of Physiology - Gastrointestinal and Liver Physiology
Volume
323
Issue
2
Start Page
G114
End Page
G125
Rights Holder(s)
SCOPUS
Bibliographic Citation
American Journal of Physiology - Gastrointestinal and Liver Physiology Vol.323 No.2 (2022) , G114-G125
Suggested Citation
Suriguga S., Li M., Luangmonkong T., Boersema M., De Jong K.P., Oosterhuis D., Gorter A.R., Beljaars L., Olinga P. Distinct responses between healthy and cirrhotic human livers upon lipopolysaccharide challenge: Possible implications for acute-on-chronic liver failure. American Journal of Physiology - Gastrointestinal and Liver Physiology Vol.323 No.2 (2022) , G114-G125. G125. doi:10.1152/ajpgi.00243.2021 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83655
Title
Distinct responses between healthy and cirrhotic human livers upon lipopolysaccharide challenge: Possible implications for acute-on-chronic liver failure
Other Contributor(s)
Abstract
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 toward insults in cirrhotic compared with 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 (PCLSs) upon the lipopolysaccharide (LPS) challenge. PCLSs prepared from livers of patients with cirrhosis or healthy donors of liver transplantation were incubated ex vivo with or without LPS for up to 48 h. Viability test, qRT-PCR, and multiplex cytokine assay were performed. Regulation of the LPS receptors during incubation or with LPS challenge differed between healthy versus cirrhotic PCLSs. LPS upregulated TLR-2 in healthy PCLSs solely (P < 0.01). Culturing for 48 h induced a stronger inflammatory response in the cirrhotic than healthy PCLS. Upon LPS stimulation, cirrhotic PCLSs secreted more proinflammatory cytokines (IL-8, IL-6, TNF-α, eotaxin, and VEGF) significantly and less antiinflammatory cytokine (IL-1ra) than those of healthy. In summary, cirrhotic PCLSs released more proinflammatory and less antiinflammatory cytokines after LPS stimuli than healthy, leading to dysregulated inflammatory response. These events could possibly resemble the liver immune response in ACLF.