TGF-beta 1 suppresses IL-6-induced STAT3 activation through regulation of Jak2 expression in prostate epithelial cells

Publikace: CELLULAR SIGNALLING 22, 1734-1744 Autoři: Starsichova, A., Lincova, E., Pernicova, Z., Kozubik, A., Soucek, K. Rok: 2010

Abstrakt

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-beta 1 (TGF-beta 1), 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-beta 1 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-beta 1 inhibits IL-6-induced expression of the cancer-associated gene MUC1. These observations demonstrated a novel interaction between TGF-beta 1 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. (C) 2010 Elsevier Inc. All rights reserved.