Influence of modulation of the actin cytoskeleton on NF-κB activation and interleukin-6 signaling

Abstract

Transcription factor NF-κB and its target gene IL6 are involved in many key processes like immune defense, inflammatory, cell proliferation and apoptosis. At the same time actin cytoskeleton plays a crucial role not only in the cell motility, but also in the proliferation and cell survival, as well as in the intracellular signal transduction. In the current work we have investigated the influence of actin cytoskeleton reorganization on the signaling pathways of NF-κB and cytokine interleukin 6 (IL-6) as well as on the proteolytic production of soluble IL-6 receptors (sIL-6R). Manipulation of the actin cytoskeleton was achieved with the help of actin-modulating substances like jasplakinolide and cytochalasins B and D. Our results showed that actin-modulating compounds do not have an effect on the phosphorylation state of NF-κB subunits p65 and RelB in the cell lines Hep3B and HCT116. Hence, perturbation of actin cytoskeleton does not lead to activation of canonical and noncanonical pathways of NF-κB. By contrast, manipulation of actin cytoskeleton with cytochalasins and jasplakinolide led to reduction in the activation of STAT3 after stimulation with IL-6 in Hep3B cells. Furthermore, production of sIL-6R by metalloprotease ADAM10 as well as synthesis of IL-6 itself was investigated. Neither the IL-6R proteolysis nor the IL-6 synthesis was affected from the used substances. In conclusion, modulation of actin cytoskeleton shows a minimal influence on the investigated processes.