Tumor necrosis factor-α induces expression and release of interleukin-6 by human urothelial cells.
Tumor necrosis factor-α induces expression and release of interleukin-6 by human urothelial cells.
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DOI:
10.1007/s00011-010-0298-x
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发表时间:
2011-06
影响因子:
6.7
通讯作者:
Bjorling, Dale E.
中科院分区:
文献类型:
--
作者:
Wang, Zun-Yi;Bjorling, Dale E.
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. HUCs were treated with TNF-α at 1–10 ng/ml for 2–24 hours. Expression of IL-6 and TNF-α receptor 1 (TNFR1) mRNAs were examined by real-time PCR. Release of IL-6 into culture medium was determined by ELISA. Presence of TNFR1 protein and TNF-α -induced activation of MAPK pathways was examined by immuoblotting analysis. The effects of selective blockers of MAPK pathway on TNF-α-induced IL-6 expression and release were determined. 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 the ERK1/2 and JNK, and TNF-α -induced IL-6 expression and release were inhibited by selective ERK1/2 and JNK blockers. These results demonstrate that TNF-α increases expression and release of IL-6 by HUCs and 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.
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