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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

International journal of molecular sciences - 22(2021), 13 vom: 02. Juli

Sprache:

Englisch

Beteiligte Personen:

Georgieva, Elizabeta [VerfasserIn]
Leber, Stefan L [VerfasserIn]
Wex, Cora [VerfasserIn]
Garbers, Christoph [VerfasserIn]

Links:

Volltext

Themen:

ADAM10 Protein
ADAM10 protein, human
Actin
Amyloid Precursor Protein Secretases
EC 3.4.-
EC 3.4.24.81
IL6 protein, human
Interleukin-6
Interleukin-6 receptor
Journal Article
Membrane Proteins
NF-κB
NF-kappa B
Receptors, Interleukin-6
STAT3
STAT3 Transcription Factor
STAT3 protein, human

Anmerkungen:

Date Completed 06.08.2021

Date Revised 06.08.2021

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms22137171

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM328265322