The transcriptomic response of rat hepatic stellate cells to endotoxin: implications for hepatic inflammation and immune regulation.

dc.contributor.author

Harvey, Stephen AK

dc.contributor.author

Dangi, Anil

dc.contributor.author

Tandon, Ashish

dc.contributor.author

Gandhi, Chandrashekhar R

dc.contributor.editor

Ryffel, Bernhard

dc.date.accessioned

2022-11-01T15:29:56Z

dc.date.available

2022-11-01T15:29:56Z

dc.date.issued

2013-01

dc.date.updated

2022-11-01T15:29:56Z

dc.description.abstract

With their location in the perisinusoidal space of Disse, hepatic stellate cells (HSCs) communicate with all of the liver cell types both by physical association (cell body as well as cytosolic processes penetrating into sinusoids through the endothelial fenestrations) and by producing several cytokines and chemokines. Bacterial lipopolysaccharide (LPS), circulating levels of which are elevated in liver diseases and transplantation, stimulates HSCs to produce increased amounts of cytokines and chemokines. Although recent research provides strong evidence for the role of HSCs in hepatic inflammation and immune regulation, the number of HSC-elaborated inflammatory and immune regulatory molecules may be much greater then known at the present time. Here we report time-dependent changes in the gene expression profile of inflammatory and immune-regulatory molecules in LPS-stimulated rat HSCs, and their validation by biochemical analyses. LPS strongly up-regulated LPS-response elements (TLR2 and TLR7) but did not affect TLR4 and down-regulated TLR9. LPS also up-regulated genes in the MAPK, NFκB, STAT, SOCS, IRAK and interferon signaling pathways, numerous CC and CXC chemokines and IL17F. Interestingly, LPS modulated genes related to TGFβ and HSC activation in a manner that would limit their activation and fibrogenic activity. The data indicate that LPS-stimulated HSCs become a major cell type in regulating hepatic inflammatory and immunological responses by altering expression of numerous relevant genes, and thus play a prominent role in hepatic pathophysiology including liver diseases and transplantation.

dc.identifier

PONE-D-13-34226

dc.identifier.issn

1932-6203

dc.identifier.issn

1932-6203

dc.identifier.uri

https://hdl.handle.net/10161/26158

dc.language

eng

dc.publisher

Public Library of Science (PLoS)

dc.relation.ispartof

PloS one

dc.relation.isversionof

10.1371/journal.pone.0082159

dc.subject

Liver

dc.subject

Animals

dc.subject

Rats

dc.subject

Rats, Sprague-Dawley

dc.subject

Inflammation

dc.subject

Mitogen-Activated Protein Kinases

dc.subject

Lipopolysaccharides

dc.subject

Transforming Growth Factor beta

dc.subject

NF-kappa B

dc.subject

RNA, Messenger

dc.subject

Chemokines

dc.subject

Signal Transduction

dc.subject

Antigen Presentation

dc.subject

Down-Regulation

dc.subject

Response Elements

dc.subject

Male

dc.subject

Toll-Like Receptors

dc.subject

Hepatic Stellate Cells

dc.subject

Transcriptome

dc.title

The transcriptomic response of rat hepatic stellate cells to endotoxin: implications for hepatic inflammation and immune regulation.

dc.type

Journal article

duke.contributor.orcid

Dangi, Anil|0000-0003-1185-3079

pubs.begin-page

e82159

pubs.issue

12

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Medicine

pubs.organisational-group

Medicine, Nephrology

pubs.publication-status

Published

pubs.volume

8

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
file.pdf
Size:
1.48 MB
Format:
Adobe Portable Document Format