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

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Abstract

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 1–10 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.

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.

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Acknowledgments

This study was supported by NIH R01 DK066349. The authors wish to thank Mrs. Yanling Chen and Marisa Chapman for technical assistance.

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Authors and Affiliations

  1. Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI, 53719, USA

    Zun-Yi Wang & Dale E. Bjorling

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  1. Zun-Yi Wang
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  2. Dale E. Bjorling
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Correspondence to Zun-Yi Wang.

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Responsible Editor: Liwu Li.

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Wang, ZY., Bjorling, D.E. Tumor necrosis factor-α induces expression and release of interleukin-6 by human urothelial cells. Inflamm. Res. 60, 525–532 (2011). https://doi.org/10.1007/s00011-010-0298-x

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  • DOI: https://doi.org/10.1007/s00011-010-0298-x

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