Perturbation of the Actin Cytoskeleton in Human Hepatoma Cells Influences Interleukin-6 (IL-6) Signaling, but Not Soluble IL-6 Receptor Generation or NF-κB Activation

Int J Mol Sci. 2021 Jul 2;22(13):7171. doi: 10.3390/ijms22137171.

Abstract

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.

Keywords: NF-κB; STAT3; actin; interleukin-6; interleukin-6 receptor.

MeSH terms

  • ADAM10 Protein / metabolism
  • Actin Cytoskeleton / metabolism*
  • Amyloid Precursor Protein Secretases / metabolism
  • Hep G2 Cells
  • Humans
  • Interleukin-6 / metabolism*
  • Membrane Proteins / metabolism
  • NF-kappa B / metabolism*
  • Receptors, Interleukin-6 / metabolism*
  • STAT3 Transcription Factor / metabolism

Substances

  • IL6 protein, human
  • Interleukin-6
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Amyloid Precursor Protein Secretases
  • ADAM10 Protein
  • ADAM10 protein, human