Chronic inflammation plays an important role in the initiation and progression of various human diseases including benign prostatic hyperplasia or prostate cancer. Here we show that the proinflammatory cytokine interleukin-6 (IL-6) has prosurvival effects and chronically activates the Jak2/STAT3 signalling pathway in a model of benign prostatic hyperplasia (BPH-1). We demonstrate that the antiinflammatory cytokine transforming growth factor-beta1 (TGF-beta1), which also permanently activates its canonical signalling pathway through SMAD proteins in BPH-1 cells, modifies the effects of IL-6 on cell proliferation. Importantly, TGF-beta1 inhibits IL-6 signal transduction by decreasing the phosphorylation levels of STAT3. This effect is associated with decreased expression of Jak2 at both mRNA and protein levels. Moreover, we showed that TGF-beta1 inhibits IL-6-induced expression of the cancer-associated gene MUC1. These observations demonstrated a novel interaction between TGF-beta1 and IL-6 signalling and suggested another mechanism of how defects in TGF-beta signalling, frequently associated with prostate pathologies, can contribute to the disruption of tissue homeostasis.
- MeSH
- buněčné linie MeSH
- epitelové buňky metabolismus MeSH
- fosforylace MeSH
- hyperplazie prostaty enzymologie metabolismus MeSH
- interleukin-6 antagonisté a inhibitory farmakologie MeSH
- Janus kinasa 2 genetika metabolismus MeSH
- lidé MeSH
- malá interferující RNA metabolismus MeSH
- mucin 1 metabolismus MeSH
- proliferace buněk MeSH
- prostata cytologie enzymologie metabolismus MeSH
- proteiny Smad metabolismus MeSH
- RNA interference MeSH
- signální transdukce MeSH
- transformující růstový faktor beta1 farmakologie MeSH
- transkripční faktor STAT3 metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antiflogistika nesteroidní farmakokinetika farmakologie MeSH
- apoptóza MeSH
- finanční podpora výzkumu jako téma MeSH
- nádorové buněčné linie účinky léků MeSH
- nádory prostaty genetika MeSH
- nádory tračníku genetika MeSH
- regulace genové exprese účinky záření MeSH
- transformující růstový faktor beta MeSH
