Potential mechanisms of action of MTA in <i>Mdr2^−/−</i> mice.

<p>Our <i>in vivo</i> and <i>in vitro</i> observations indicate that MTA displays different actions that may underlie its beneficial effects on the course of liver injury and fibrosis in <i>Mdr2^−/−</i> mice. MTA may exert a direct cytoprotective effect on hepatocytes by reducing JNK activity, preventing hepatocellular death and further inflammation. MTA also inhibits the production of cytokines by inflammatory cells, likely through interference with NFκB activity as described before <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015690#pone.0015690-Hevia1" target="_blank">[16]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015690#pone.0015690-IglesiasAra1" target="_blank">[18]</a>. In addition, enhanced expression of adenosine A2B receptors may contribute to the anti-inflammatory pharmacological profile of MTA. This compound can also exert direct effects on extracellular matrix (ECM) producing cells (myofibroblasts), reducing their activation, proliferation and the production of pro-fibrogenic factors. Inhibition of JunD expression may be an important event in the antifibrogenic action of MTA.