RESUMO
The transcription factor nuclear factor-kappa B (NF-κB) is critically involved in inflammation and cancer development. Activation of NF-κB induces the expression and release of several pro-inflammatory proteins, which include the cytokine interleukin-6 (IL-6). Perturbation of the actin cytoskeleton has been previously shown to activate NF-κB signaling. In this study, we analyze the influence of different compounds that modulate the actin cytoskeleton on NF-κB activation, IL-6 signaling and the proteolytic generation of the soluble IL-6 receptor (sIL-6R) in human hepatoma cells. We show that perturbation of the actin cytoskeleton is not sufficient to induce NF-κB activation and IL-6 secretion. However, perturbation of the actin cytoskeleton reduces IL-6-induced activation of the transcription factor STAT3 in Hep3B cells. In contrast, IL-6R proteolysis by the metalloprotease ADAM10 did not depend upon the integrity of the actin cytoskeleton. In summary, we uncover a previously unknown function of the actin cytoskeleton in IL-6-mediated signal transduction in Hep3B cells.