PMID- 15860640
OWN - NLM
STAT- MEDLINE
DCOM- 20050913
LR  - 20061115
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 289
IP  - 3
DP  - 2005 Sep
TI  - Exposure to bacterial cell wall products triggers an inflammatory phenotype in 
      hepatic stellate cells.
PG  - G571-8
AB  - 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.
FAU - Brun, Paola
AU  - Brun P
AD  - Department of Histology, University of Padua, Padua, Italy.
FAU - Castagliuolo, Ignazio
AU  - Castagliuolo I
FAU - Pinzani, Massimo
AU  - Pinzani M
FAU - Palu, Giorgio
AU  - Palu G
FAU - Martines, Diego
AU  - Martines D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050428
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Bacterial Toxins)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Teichoic Acids)
RN  - 56411-57-5 (lipoteichoic acid)
SB  - IM
MH  - Animals
MH  - Bacterial Toxins/*metabolism/*toxicity
MH  - Cell Wall
MH  - Cytokines/biosynthesis
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Profiling
MH  - Immunohistochemistry
MH  - *Inflammation
MH  - Lipopolysaccharides/toxicity
MH  - Liver/*cytology/immunology/*pathology
MH  - Liver Cirrhosis/physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Phenotype
MH  - Portal Vein
MH  - RNA, Messenger/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Teichoic Acids/toxicity
MH  - Up-Regulation
EDAT- 2005/04/30 09:00
MHDA- 2005/09/15 09:00
CRDT- 2005/04/30 09:00
PHST- 2005/04/30 09:00 [pubmed]
PHST- 2005/09/15 09:00 [medline]
PHST- 2005/04/30 09:00 [entrez]
AID - 00537.2004 [pii]
AID - 10.1152/ajpgi.00537.2004 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2005 Sep;289(3):G571-8. doi: 
      10.1152/ajpgi.00537.2004. Epub 2005 Apr 28.