Tumor necrosis factor-α induces expression and release of interleukin-6 by human urothelial cells

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 h. 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.

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.

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.