Cited 581 times in
Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 백용한 | - |
dc.date.accessioned | 2015-07-15T16:41:31Z | - |
dc.date.available | 2015-07-15T16:41:31Z | - |
dc.date.issued | 2003 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/113405 | - |
dc.description.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 proinflammatory gene expression in activated human HSCs. Culture-activated HSCs and HSCs isolated from patients with hepatitis C virus-induced cirrhosis express LPS-associated signaling molecules, including CD14, toll-like receptor (TLR) 4, and MD2. Stimulation of culture-activated HSCs with LPS results in a rapid and marked activation of NF-κB, as assessed by in vitro kinase assays for IκB kinase (IKK), IκBα steady-state levels, p65 nuclear translocation, NF-κB-dependent luciferase reporter gene assays, and electrophoretic mobility shift assays. Lipid A induces NF-κB activation in a similar manner. Both LPS- and lipid A-induced NF-κB activation is blocked by preincubation with either anti-TLR4 blocking antibody (HTA125) or Polymyxin B. Lipid A induces NF-κB activation in HSCs from TLR4-sufficient (C3H/OuJ) mice but not from TLR4-deficient (C3H/HeJ) mice. LPS also activates c-Jun N-terminal kinase (JNK), as assessed by in vitro kinase assays. LPS up-regulates IL-8 and MCP-1 gene expression and secretion. 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 up-regulates cell surface expression of ICAM-1 and VCAM-1. In conclusion, human activated HSCs utilize components of TLR4 signal transduction cascade to stimulate NF-κB and JNK and up-regulate chemokines and adhesion molecules. Thus, HSCs are a potential mediator of LPS-induced liver injury. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 1043~1055 | - |
dc.relation.isPartOf | HEPATOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Blood Proteins/pharmacology | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Chemokine CCL2/metabolism | - |
dc.subject.MESH | Drosophila Proteins* | - |
dc.subject.MESH | Hepatocytes/cytology | - |
dc.subject.MESH | Hepatocytes/physiology* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Intercellular Adhesion Molecule-1/metabolism | - |
dc.subject.MESH | Interleukin-8/metabolism | - |
dc.subject.MESH | JNK Mitogen-Activated Protein Kinases | - |
dc.subject.MESH | Lipopolysaccharide Receptors/genetics | - |
dc.subject.MESH | Lipopolysaccharide Receptors/metabolism | - |
dc.subject.MESH | Lipopolysaccharides/pharmacology* | - |
dc.subject.MESH | Liver Cirrhosis/immunology | - |
dc.subject.MESH | Liver Cirrhosis/metabolism* | - |
dc.subject.MESH | Membrane Glycoproteins/genetics | - |
dc.subject.MESH | Membrane Glycoproteins/metabolism* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred C3H | - |
dc.subject.MESH | Mitogen-Activated Protein Kinases/metabolism | - |
dc.subject.MESH | NF-kappa B/metabolism | - |
dc.subject.MESH | Receptors, Cell Surface/genetics | - |
dc.subject.MESH | Receptors, Cell Surface/metabolism* | - |
dc.subject.MESH | Signal Transduction/drug effects | - |
dc.subject.MESH | Signal Transduction/immunology* | - |
dc.subject.MESH | Toll-Like Receptor 4 | - |
dc.subject.MESH | Toll-Like Receptors | - |
dc.subject.MESH | Transcription Factor AP-1/metabolism | - |
dc.subject.MESH | Up-Regulation/drug effects | - |
dc.subject.MESH | Up-Regulation/immunology | - |
dc.subject.MESH | Vascular Cell Adhesion Molecule-1/metabolism | - |
dc.title | Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Yong-Han Paik | - |
dc.contributor.googleauthor | Robert F. Schwabe | - |
dc.contributor.googleauthor | David A. Brenner | - |
dc.contributor.googleauthor | Christian Jobin | - |
dc.contributor.googleauthor | Maria P. Russo | - |
dc.contributor.googleauthor | Ramón Bataller | - |
dc.identifier.doi | 10.1053/jhep.2003.50182 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01829 | - |
dc.relation.journalcode | J00985 | - |
dc.identifier.eissn | 1527-3350 | - |
dc.identifier.pmid | 12717385 | - |
dc.identifier.url | http://onlinelibrary.wiley.com/doi/10.1053/jhep.2003.50182/abstract | - |
dc.subject.keyword | 12717385 | - |
dc.contributor.alternativeName | Paik, Yong Han | - |
dc.contributor.affiliatedAuthor | Paik, Yong Han | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 37 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 1043 | - |
dc.citation.endPage | 1055 | - |
dc.identifier.bibliographicCitation | HEPATOLOGY, Vol.37(5) : 1043-1055, 2003 | - |
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