title: TGF-beta1 suppresses IL-6-induced STAT3 activation through regulation of Jak2 expression in prostate epithelial cells.
abstract: 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.
authors.affiliation: Department of Cytokinetics, Institute of Biophysics, Acad Sci Czech Rep, Královopolská 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Andrea
authors.initials: A
authors.lastname: Starsíchová
authors.forename: Eva
authors.initials: E
authors.lastname: Lincová
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Pernicová
authors.forename: Alois
authors.initials: A
authors.lastname: Kozubík
authors.forename: Karel
authors.initials: K
authors.lastname: Soucek
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018396:Mucin-1 / Q000378:metabolism; D010766:Phosphorylation; D011467:Prostate / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D015850:Interleukin-6; D053614:Janus Kinase 2; D018396:Mucin-1; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D000093242:Interleukin-6 Inhibitors; C060192:MUC1 protein, human; C494086:STAT3 protein, human