caa a22 4500 445884975 CHVBK 20180317145556.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00011-010-0298-x doi (NATIONALLICENCE)springer-10.1007/s00011-010-0298-x Tumor necrosis factor-α induces expression and release of interleukin-6 by human urothelial cells [Elektronische Daten] [Zun-Yi Wang, Dale Bjorling] Objective: We examined the effects of tumor necrosis factor-α (TNF-α) on expression and release of interleukin-6 (IL-6) by human urothelial cells (HUCs) and investigated whether the effects of TNF-α are mediated by mitogen-activated protein kinase (MAPK) pathways. Materials and methods: HUCs were treated with TNF-α at 1-10ng/ml for 2-24h. Expression of IL-6 and TNF-α receptor 1 (TNFR1) mRNAs were examined by real-time PCR. The release of IL-6 into culture medium was determined by ELISA. The presence of TNFR1 protein and TNF-α-induced activation of MAPK pathways was examined by immunoblotting analysis. The effects of selective blockers of MAPK pathways on TNF-α-induced IL-6 expression and release were determined. Results: TNF-α increased IL-6 mRNA expression and stimulated release of IL-6 in a concentration- and time-dependent manner. The effects of TNF-α were mediated by TNFR1. TNF-α induced phosphorylation of ERK1/2 and JNK, and TNF-α-induced IL-6 expression and release were inhibited by selective ERK1/2 and JNK blockers. Conclusions: These results demonstrate that TNF-α increases expression and release of IL-6 by HUCs and that the effects of TNF-α are mediated by TNFR1. Also, the ERK1/2 and JNK pathways are involved in TNF-α-induced expression and release of IL-6 in HUCs and may represent therapeutic targets in inflammatory urinary tract diseases. Springer Basel AG, 2010 Tumor necrosis factor-α nationallicence Interleukin-6 nationallicence Urothelial cells nationallicence Mitogen-activated protein kinase nationallicence Wang Zun-Yi Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, 53719, Madison, WI, USA aut Bjorling Dale Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, 53719, Madison, WI, USA aut Inflammation Research SP Birkhäuser Verlag Basel 60/6(2011-06-01), 525-532 1023-3830 60:6<525 2011 60 11 https://doi.org/10.1007/s00011-010-0298-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-010-0298-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Zun-Yi Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, 53719, Madison, WI, USA aut NATIONALLICENCE 700 1- Bjorling Dale Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, 53719, Madison, WI, USA aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/6(2011-06-01), 525-532 1023-3830 60:6<525 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer