IL-17 and TNFα cooperation contributes to the pro-inflammatory response of hepatic stellate cells.
Authors of this article are:
Beringer A, Miossec P.
A summary of the article is shown below:
Hepatic stellate cells (HSCs) have a central role in liver inflammation and fibrosis by producing inflammatory and fibrotic mediators. Their activation is regulated through direct cell-cell interactions but also through systemic and local effects of soluble factors, such as cytokines. The effects of the pro-inflammatory cytokines IL-17 and TNFα and cell interactions with hepatocytes on HSC activation were assessed. Human HSC and HepaRG cells were exposed to IL-17 and/or TNFα. IL-17 and TNFα contribution from immune cells was determined in a co-culture model with phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC), HSC and/or hepatocytes. IL-17 enhanced TNFα effects on the induction of IL-6, IL-1β, and the chemokine IL-8, CCL20 and MCP-1 expression/secretion in isolated HSC cultures. HSC-hepatocyte interactions did not enhance IL-6, IL-8 and CCL20 production compared to hepatocyte alone. However, HSC-hepatocyte interactions increased C-reactive protein expression. IL-17 and/or TNFα had no direct pro-fibrotic effects on collagen 1 α1, TIMP and MMP2 gene expression whereas mRNA levels of MMP3, an enzyme involved in matrix destruction, were up-regulated in HSCs. The use of specific inhibitors of IL-17 and TNFα indicated their contribution to the strong increase of IL-6 and IL-8 production induced by PBMC, HSC and/or hepatocyte interactions. As chronic liver inflammation leads to liver fibrosis, IL-17 and/or TNFα neutralization can be of interest to control liver inflammation and therefore its effects on fibrosis. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
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This article is a good source of information and a good way to become familiar with topics such as: cell interactions; hepatic stellate cells; inflammation; interleukin-17; tumor necrosis factor-α.