Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure

Abstract Objectives Toll-like receptors (TLRs) on neutrophils play a crucial role in detecting pathogens and organ/tissue injury in acute-on-chronic liver failure (ACLF). However, little is known about the exact mechanisms and potential signalling pathways. The aim of this study was to investigate a...

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Autores principales:	Yi Zhang, Wei Wu, Yijie Wang, Lingjia Tong, Meng Hong, Qi Xia, Zhi Chen
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Toll-like receptors mRNA Pathogens and organ/tissue injury Acute-on-chronic liver failure Neutrophil Medicine R
Acceso en línea:	https://doaj.org/article/919b5891c00e4dcab5043f0adc69bbe2
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spelling	oai:doaj.org-article:919b5891c00e4dcab5043f0adc69bbe22021-11-14T12:08:16ZGene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure10.1186/s12967-021-03135-31479-5876https://doaj.org/article/919b5891c00e4dcab5043f0adc69bbe22021-11-01T00:00:00Zhttps://doi.org/10.1186/s12967-021-03135-3https://doaj.org/toc/1479-5876Abstract Objectives Toll-like receptors (TLRs) on neutrophils play a crucial role in detecting pathogens and organ/tissue injury in acute-on-chronic liver failure (ACLF). However, little is known about the exact mechanisms and potential signalling pathways. The aim of this study was to investigate alterations in TLR signalling pathways in neutrophils of ACLF patients. Methods Twenty-seven patients with compensated cirrhosis (n = 9), decompensated cirrhosis (n = 9) and ACLF (n = 9) were enrolled in the study. Neutrophils were isolated, and alterations in TLR signalling pathways were evaluated using an RT2 Profiler™ PCR Array. The fold change for each gene (2(−∆∆CT)) was compared among the groups. Genes with a fold change ratio of ≥ 2 or ≤ 0.5 along with a p value of < 0.05 were considered to be differentially expressed. Results A total of 17 genes were upregulated in neutrophils from patients with compensated cirrhosis and were mainly distributed in adaptors, TLR-interacting proteins and downstream pathways. Six genes were detected in patients with decompensated cirrhosis. A trend of downregulation of genes in the TLR signalling pathway was observed in neutrophils of patients with cirrhosis and ACLF. TLR3, IFNG, IL1B, TBK1, CCL2 and LTA were downregulated in neutrophils. Moreover, CD14 and IL10 were upregulated in neutrophils of ACLF patients. Conclusions TLR signalling pathway genes were differentially regulated in neutrophils between cirrhosis and ACLF. In ACLF patients, defective expression of TLR3 and IFN, along with enhanced CD14 and IL10 expression, was characterized by transcriptional alterations of neutrophils.Yi ZhangWei WuYijie WangLingjia TongMeng HongQi XiaZhi ChenBMCarticleToll-like receptorsmRNAPathogens and organ/tissue injuryAcute-on-chronic liver failureNeutrophilMedicineRENJournal of Translational Medicine, Vol 19, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Toll-like receptors mRNA Pathogens and organ/tissue injury Acute-on-chronic liver failure Neutrophil Medicine R
spellingShingle	Toll-like receptors mRNA Pathogens and organ/tissue injury Acute-on-chronic liver failure Neutrophil Medicine R Yi Zhang Wei Wu Yijie Wang Lingjia Tong Meng Hong Qi Xia Zhi Chen Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure
description	Abstract Objectives Toll-like receptors (TLRs) on neutrophils play a crucial role in detecting pathogens and organ/tissue injury in acute-on-chronic liver failure (ACLF). However, little is known about the exact mechanisms and potential signalling pathways. The aim of this study was to investigate alterations in TLR signalling pathways in neutrophils of ACLF patients. Methods Twenty-seven patients with compensated cirrhosis (n = 9), decompensated cirrhosis (n = 9) and ACLF (n = 9) were enrolled in the study. Neutrophils were isolated, and alterations in TLR signalling pathways were evaluated using an RT2 Profiler™ PCR Array. The fold change for each gene (2(−∆∆CT)) was compared among the groups. Genes with a fold change ratio of ≥ 2 or ≤ 0.5 along with a p value of < 0.05 were considered to be differentially expressed. Results A total of 17 genes were upregulated in neutrophils from patients with compensated cirrhosis and were mainly distributed in adaptors, TLR-interacting proteins and downstream pathways. Six genes were detected in patients with decompensated cirrhosis. A trend of downregulation of genes in the TLR signalling pathway was observed in neutrophils of patients with cirrhosis and ACLF. TLR3, IFNG, IL1B, TBK1, CCL2 and LTA were downregulated in neutrophils. Moreover, CD14 and IL10 were upregulated in neutrophils of ACLF patients. Conclusions TLR signalling pathway genes were differentially regulated in neutrophils between cirrhosis and ACLF. In ACLF patients, defective expression of TLR3 and IFN, along with enhanced CD14 and IL10 expression, was characterized by transcriptional alterations of neutrophils.
format	article
author	Yi Zhang Wei Wu Yijie Wang Lingjia Tong Meng Hong Qi Xia Zhi Chen
author_facet	Yi Zhang Wei Wu Yijie Wang Lingjia Tong Meng Hong Qi Xia Zhi Chen
author_sort	Yi Zhang
title	Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure
title_short	Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure
title_full	Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure
title_fullStr	Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure
title_full_unstemmed	Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure
title_sort	gene profiling of toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure
publisher	BMC
publishDate	2021
url	https://doaj.org/article/919b5891c00e4dcab5043f0adc69bbe2
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Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure

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