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Induction of an Inflammatory Response in Primary Hepatocyte Cultures from Mice
Published on: March 10, 2017
Hepatocyte growth factor induces delayed STAT3 phosphorylation through interleukin-6 expression.
Bok-Soon Lee1, Minseon Park, Hyun-Young Cha
1Department of Biochemistry and Molecular Biology, Ajou University Medical School, 5 Wonchon-Dong, Yeongtong-Gu, Suwon 443-721, South Korea.
Cellular Signalling
|December 17, 2008
Summary
Hepatocyte growth factor (HGF/SF) signaling activates STAT3 phosphorylation indirectly. This delayed effect is mediated by newly synthesized interleukin-6 (IL-6), highlighting a novel pathway involving PI3 kinase.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Signal Transduction
Background:
- Met receptor tyrosine kinase activation by HGF/SF triggers cellular responses.
- STAT3 is a known downstream target of HGF/SF-Met signaling.
Purpose of the Study:
- To investigate the mechanism behind delayed STAT3 phosphorylation following HGF/SF stimulation.
- To identify the specific mediators involved in the HGF/SF-Met signaling pathway.
Main Methods:
- Cell treatment with HGF/SF in NIH3T3 and Chang liver cells.
- Inhibition studies using cycloheximide, actinomycin D, and neutralizing IL-6 antibody.
- Analysis of STAT3 phosphorylation and IL-6 production.
- Pharmacological inhibition of PI3 kinase pathway using LY294002.
Main Results:
- HGF/SF treatment induced a delayed phosphorylation of STAT3 (Tyr705).
- Newly synthesized secretory protein, identified as IL-6, was responsible for the delayed STAT3 phosphorylation.
- IL-6 production and accumulation were observed after HGF/SF stimulation.
- PI3 kinase pathway inhibition abolished the delayed STAT3 phosphorylation, while other inhibitors did not.
Conclusions:
- HGF/SF-Met signaling cascade stimulates IL-6 production via the PI3 kinase pathway.
- IL-6 acts as a secondary mediator, leading to STAT3 phosphorylation.
- This study reveals a novel indirect mechanism for STAT3 activation downstream of HGF/SF-Met signaling.
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