Role of IL-6 trans-signaling in CCl₄induced liver damage
| Autor: | Jessica, Gewiese-Rabsch, Claudia, Drucker, Sven, Malchow, Jürgen, Scheller, Stefan, Rose-John |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Interleukin-6 Neutrophils Liver Diseases Recombinant Fusion Proteins Blotting Western Cytochrome P-450 CYP2E1 Enzyme-Linked Immunosorbent Assay Receptors Interleukin-6 Thiobarbituric Acid Reactive Substances Up-Regulation Mice Inbred C57BL Mice Liver Cytokine Receptor gp130 Animals Carbon Tetrachloride Glycogen Signal Transduction |
| Zdroj: | Biochimica et biophysica acta. 1802(11) |
| ISSN: | 0006-3002 |
| Popis: | Interleukin-6 (IL-6) plays an important role in liver regeneration and protection against liver damage. In addition to IL-6 classic signaling via membrane bound receptor (mIL-6R), IL-6 signaling can also be mediated by soluble IL-6R (sIL-6R) thereby activating cells that do not express membrane bound IL-6R. This process has been named trans-signaling. IL-6 trans-signaling has been demonstrated to operate during liver regeneration. We have developed methods to specifically block or mimic IL-6 trans-signaling. A soluble gp130 protein (sgp130Fc) exclusively inhibits IL-6 trans-signaling whereas an IL-6/sIL-6R fusion protein (Hyper-IL-6) mimics IL-6 trans-signaling. Using these tools we investigate the role of IL-6 trans-signaling in CCl₄ induced liver damage. Blockade of IL-6 trans-signaling during CCl₄ induced liver damage led to higher liver damage, although induction of Cyp4502E1 and thus bioactivation of CCl₄ was unchanged. Depletion of neutrophils resulted in reduced liver transaminase levels irrespective of IL-6 trans-signaling blockade. Furthermore, IL-6 trans-signaling was important for refilling of hepatocyte glycogen stores, which were depleted 24 h after CCl₄ treatment. We conclude that IL-6 trans-signaling via the soluble IL-6R is important for the physiologic response of the liver to CCl₄ induced chemical damage. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|