title: Tumor necrosis factor-α induces expression and release of interleukin-6 by human urothelial cells.
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.
  
  
  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.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53719, USA. wangz@svm.vetmed.wisc.edu
authors.forename: Zun-Yi
authors.initials: ZY
authors.lastname: Wang
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bjorling
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019459:Urothelium / Q000166:cytology / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases