Toll-like receptor 4 mediated inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells
Year: 2004
Type: dissertation
Abstract: Bacterial lipopolysaccharide (LPS) stimulates Kupffer cells and participates in the pathogenesis of alcohol-induced liver injury.However, it is unknown whether LPS directly affects hepatic stellate cells (HSCs), the main fibrogenic cell type in the injured liver.This study characterizes LPS-induced signal transduction and pro-inflammatory gene expression in activated human HSCs.Human HSCs were isolated and activated in culture.Expressions of CD14, Toll-like receptor (TLR) 4, and MD2 mRNA were assessed by RT-PCR.IκBα and phospho-c-Jun were assessed by Western blot analysis.IκBα kinase (IKK) and c-Jun N-terminal sufficient mice) but not from C3H/HeJ (TLR4-deficient mice).LPS also activates c-Jun N-terminal Kinase (JNK).LPS upregulates gene expression and secretion of IL-8 and MCP-1.LPS-induced IL-8 secretion is completely inhibited by the IκB super-repressor (Ad5IκB) and partially inhibited by a specific JNK inhibitor, SP600125.LPS also upregulates cell surface expression of ICAM-1 and VCAM-1.Human activated HSCs utilize components of TLR4 signal transduction cascade to stimulate NF-κB and JNK, and upregulate chemokines and adhesion molecules.Thus, HSCs are a potential mediator of LPS-induced liver injury.
Author: 諛깆슜�븳
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7025134309