title: Effects of interleukin 18 on injury and activation of human proximal tubular epithelial cells.
abstract: OBJECTIVE
  Injury and activation of tubular proximal epithelial cells (TEC) play central roles in renal tubulointerstitial fibrosis (TIF), but its mechanisms remain obscure. Interleukin 18 (IL-18) is overproduced during chronic kidney diseases (CKD), but how IL-18 affects the biological behaviour of TEC is not clear. The aim of the present study is to reveal the role of IL-18 in renal TIF.
  
  
  METHODS
  The expressions of IL-18 and IL-18 receptor in TEC were detected by immunohistochemical staining in vivo and by reverse transcriptase polymerase chain reaction (RT-PCR) in vitro. TEC line (HK-2 cells) were incubated without or with IL-18. Cell proliferation and cell cycle were evaluated by methyl thiazolyl tetrazolium assay and flow cytometric analysis, respectively. Cell apoptosis was assessed by Hoechst 33258 staining. Expression of alpha-smooth muscle actin was evaluated by RT-PCR, immunocytochemical staining and flow cytometric analysis, respectively. Type I collagen, fibronectin, MCP-1 and RANTES in cultured supernatants were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  IL-18 expression in TEC increased significantly in CKD state. IL-18 receptor was constitutively expressed in normal proximal TEC, and its expression increased strongly in CKD state. Proliferation and cell cycle of HK-2 cells were not affected by IL-18. Cell apoptosis, alpha-smooth muscle actin expression, type I collagen and fibronectin production as well as MCP-1 secretion were promoted by IL-18 in dosage- and/or time-dependent manners, but RANTES secretion was not affected.
  
  
  CONCLUSIONS
  IL-18 may play a crucial role in the process of TIF by promoting TEC injury and activation, and could be a target of the therapeutic approaches against TIF.
authors.affiliation: Institute of Nephrology, Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.forename: Hua-Feng
authors.initials: HF
authors.lastname: Liu
authors.forename: Cui-Wei
authors.initials: CW
authors.lastname: Yao
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Liu
authors.forename: Chang-Mei
authors.initials: CM
authors.lastname: Huang-Fu
authors.forename: Xiang-Wen
authors.initials: XW
authors.lastname: Chen
authors.forename: Shen-Hua
authors.initials: SH
authors.lastname: Du
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Chen
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D018932:Chemokine CCL2 / Q000032:analysis; D018946:Chemokine CCL5 / Q000032:analysis; D024042:Collagen Type I / Q000032:analysis; D003470:Culture Media / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000378:metabolism* / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D053724:Receptors, Interleukin-18 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D024042:Collagen Type I; D003470:Culture Media; D005353:Fibronectins; D020382:Interleukin-18; D012333:RNA, Messenger; D053724:Receptors, Interleukin-18