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

PloS One
Stephen A K HarveyChandrashekhar R Gandhi

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 T...Continue Reading

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Citations

Jun 3, 2015·Journal of Cellular Physiology·Anil DangiChandrashekhar R Gandhi
Jul 5, 2016·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Naglaa A BayomyEman Z Abdelaziz
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Feb 18, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Akanksha SharmaChandrashekhar R Gandhi
Sep 25, 2017·Journal of Hepatology·Chandrashekhar R Gandhi
Apr 2, 2018·Gastroenterología y hepatología·Braira WahidMuhammad Idrees

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Methods Mentioned

BETA
ELISArray
ELISA
nuclear translocation
FACS
flow cytometry

Software Mentioned

Mapk
Affymetrix GCOS
excel
GCOS
IPA
Ingenuity Pathway Analysis

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