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Exposure to bacterial cell wall products triggers an inflammatory phenotype in hepatic stellate cells

Activated hepatic stellate cells (HSCs) secrete extracellular matrix components during hepatic fibrosis, but recent studies have shown that HSCs can also release a variety of proinflammatory cytokines. Moreover, bacterial endotoxemia is not only associated with systemic complications in the late sta...

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Published in:American journal of physiology: Gastrointestinal and liver physiology 2005-09, Vol.289 (3), p.G571-G578
Main Authors: Brun, Paola, Castagliuolo, Ignazio, Pinzani, Massimo, Palù, Giorgio, Martines, Diego
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cited_by cdi_FETCH-LOGICAL-c363t-427938052c1906420f7fb018e93910264a982c2c7d369c8f875512187d7774583
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container_start_page G571
container_title American journal of physiology: Gastrointestinal and liver physiology
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creator Brun, Paola
Castagliuolo, Ignazio
Pinzani, Massimo
Palù, Giorgio
Martines, Diego
description Activated hepatic stellate cells (HSCs) secrete extracellular matrix components during hepatic fibrosis, but recent studies have shown that HSCs can also release a variety of proinflammatory cytokines. Moreover, bacterial endotoxemia is not only associated with systemic complications in the late stages of liver failure but is also a direct cause of liver damage, activating resident inflammatory cells. In this study, we investigated whether HSCs can respond directly to bacterial cell wall products acquiring a new phenotype. RT-PCR and immunocytochemistry assays were used to show that murine HSCs expressed specific mRNA transcripts and proteins for LPS and lipoteichoic acid (LTA) receptor systems and peptidoglycan recognition proteins. Exposing HSCs to bacterial endotoxins led to phosphorylation of mitogen-activated protein kinase ERK1 and the development of a proinflammatory phenotype. After exposure to LPS, LTA, or N-acetyl muramyl peptide, transforming growth factor-beta1, IL-6, and monocyte chemoattractant protein-1 (MCP-1) mRNA specific transcripts and proteins increased significantly in HSCs, as assayed by quantitative real-time RT-PCR and ELISA. These LPS-mediated effects in HSCs were receptor dependent, because LPS-induced ERK1 phosphorylation, IL-6, and MCP-1 mRNA and protein level upregulation were significantly less pronounced in HSCs isolated from C3H/HeJ mice lacking Toll-like receptor 4. In conclusion, our results show that murine HSCs express functional receptors for bacterial endotoxins, and HSCs exposed to bacterial products develop a strong proinflammatory phenotype. We speculate that high levels of bacterial endotoxins in the portal vein may directly induce a proinflammatory phenotype in HSCs that contributes to liver damage.
doi_str_mv 10.1152/ajpgi.00537.2004
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These LPS-mediated effects in HSCs were receptor dependent, because LPS-induced ERK1 phosphorylation, IL-6, and MCP-1 mRNA and protein level upregulation were significantly less pronounced in HSCs isolated from C3H/HeJ mice lacking Toll-like receptor 4. In conclusion, our results show that murine HSCs express functional receptors for bacterial endotoxins, and HSCs exposed to bacterial products develop a strong proinflammatory phenotype. 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subjects Animals
Bacterial Toxins - metabolism
Bacterial Toxins - toxicity
Cell Wall
Cytokines - biosynthesis
Enzyme-Linked Immunosorbent Assay
Gene Expression Profiling
Immunohistochemistry
Inflammation
Lipopolysaccharides - toxicity
Liver - cytology
Liver - immunology
Liver - pathology
Liver Cirrhosis - physiopathology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Phenotype
Portal Vein
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
Teichoic Acids - toxicity
Up-Regulation
title Exposure to bacterial cell wall products triggers an inflammatory phenotype in hepatic stellate cells
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