Schnabl, Bernd and Brandl, Katharina and Fink, Marina and Gross, Philipp and Taura, Kojiro and Gaebele, Erwin and Hellerbrand, Claus and Falk, Werner (2008) A TLR4/MD2 fusion protein inhibits LPS-induced pro-inflammatory signaling in hepatic stellate cells. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 375 (2). pp. 210-214. ISSN 0006-291X,
Full text not available from this repository. (Request a copy)Abstract
Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. In injured liver they are the main extracellular matrix protein producing cell type and further perpetuate hepatic injury by secretion of pro-inflammatory mediators. Since LPS-mediated signaling through toll-like receptor 4 (TLR4) has been identified as key fibrogenic signal in HSCs we aimed to test TLR4 as potential target of therapy via ligand-binding Soluble receptors. Incubation Of human HSCs with a fusion protein between the extracellular domain of TLR4 and MD2 which binds LPS inhibited LPS-induced NF kappa B and JNK activation. TLR4/MD2 abolished LPS-induced secretion of IL-6, IL-8, MCPI, and RANTES in HSCs. In addition, TLR4/MD2 fused to human IgG-Fc neutralized LPS activity. Since TLR4 Mutant mice are resistant to liver fibrosis, the TLR4/MD2 soluble receptor might represent a new therapeutic molecule for liver fibrogenesis in vivo. (c) 2008 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; ACTIVATION; FIBROGENESIS; EXPRESSION; ENDOTOXIN; CIRRHOSIS; FIBROSIS; COMPLEX; MD-2; LPS; toll-like receptor; hepatic stellate cells; liver fibrosis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Oct 2020 10:06 |
| Last Modified: | 21 Oct 2020 10:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30171 |
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