TGF-ß1 suppresses IL-6-induced STAT3 activation through regulation of Jak2 expression in prostate epithelial cells

Konference: 2010 6. sympózium a workshop molekulární patologie a histo-cyto-chemie

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Workshop on Molecular Pathology

Číslo abstraktu: w003

Autoři: Andrea Staršíchová; Eva Lincová; Mgr. Zuzana Pernicová; prof. RNDr. Alois Kozubík, CSc.; Mgr. Karel Souček, Ph.D.

Chronic inflammation plays an important role in initiation and progression of various human diseases including benign prostatic hyperplasia or prostate cancer. Here, we show that proinflammatory cytokine interleukin-6 (IL-6) has prosurvival effects and chronically activates Jak2/STAT3 signaling pathway in a model of benign prostatic hyperplasia. We demonstrate that anti-inflammatory cytokine transforming growth factor ßi (TGF-ß1), which also permanently activates its canonical signaling pathway through SMAD proteins in BPH-1 cells, affects the effects of IL-6 on cell proliferation. Moreover and importantly, TGF-ß1 inhibits IL-6 signal transduction (during longtime action of both cytokines) by decreasing phosphorylation levels of STAT3 and decreases nuclear localization of phosphorylated STAT3 as well. This is associated with reduced expression of Jak2 at both mRNA and protein levels. In conclusion, our data show that TGF-ß1 reverts prosurvival effects of IL-6 through regulation of Jak2 expression in prostate epithelial cells.

Datum přednesení příspěvku: 24. 4. 2010