TGF-β1 suppresses IL-6-induced STAT3 activation through regulation of Jak2 expression in prostate epithelial cells

被引:32
作者
Starsichova, Andrea [1 ]
Lincova, Eva [1 ,2 ]
Pernicova, Zuzana [1 ,2 ]
Kozubik, Alois [1 ,2 ]
Soucek, Karel [1 ,2 ]
机构
[1] Acad Sci Czech Rep, Inst Biophys, Dept Cytokinet, CZ-61265 Brno, Czech Republic
[2] Masaryk Univ, Fac Sci, Dept Expt Biol, CZ-61137 Brno, Czech Republic
关键词
Interleukin-6; Transforming growth factor-beta; Janus kinase-2; Mucin-1; Prostate; Epithelial cells; SIGNAL TRANSDUCER GP130; TGF-BETA; CANCER; INTERLEUKIN-6; PROGRESSION; GENE; TUMORIGENESIS; INFLAMMATION; HYPERPLASIA; DISEASE;
D O I
10.1016/j.cellsig.2010.06.014
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1734 / 1744
页数:11
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