title: LPS-evoked IL-18 expression in mesangial cells plays a role in accelerating lupus nephritis.
abstract: OBJECTIVE
  Systemic lupus erythematosus is occasionally accompanied with bacterial infection. Lipopolysaccharide (LPS) from bacteria can accelerate and exacerbate lupus nephritis (LN) in animal models, but some mechanisms underlying the LPS-induced acceleration are still unclear. First, it is not known whether LPS can stimulate mesangial cells (MCs) to secrete the pro-inflammatory cytokine, interleukin (IL)-18. Second, it is also unclear whether LPS and/or IL-18 can induce MC apoptosis. Here, we attempted to clarify the cause-and-effect relationships between LPS stimulation, IL-18 production and MC apoptosis to address the above questions.
  
  
  METHODS
  LPS was used to induce accelerated LN in LN-prone mice. LPS and IL-18 were also used to treat cultured MCs isolated from the mice. IL-18 expression and MC apoptosis were investigated by in situ hybridization, the TUNEL method, reverse transcription- polymerase chain reaction (RT-PCR), western blotting, DNA electrophoresis and flow cytometry. NFkappaB was detected by immunofluorescent staining.
  
  
  RESULTS
  In the LPS-accelerated LN mice, we observed co-existence of IL-18 expression, hyperplasia, apoptosis, and activated apoptotic signal transduction in MCs, as well as marked neutrophil infiltration in the glomerulus, especially around the mesangial region. In cultured MCs, LPS greatly enhanced IL-18 expression, but did not induce apoptosis, while mouse IL-18 did not induce apoptosis or activate apoptotic signal transduction in MCs.
  
  
  CONCLUSIONS
  We conclude that LPS can evoke IL-18 production in MCs, but neither LPS nor IL-18 directly induces apoptosis or activates apoptotic signal transduction in the cells. We infer that LPS-induced IL-18 production by MCs could be a mediator by which LPS accelerates and exacerbates LN.
authors.affiliation: Graduate Institute of Medical Sciences, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Gung Road, Taipei, Taiwan, ROC.
authors.forename: H-A
authors.initials: HA
authors.lastname: Shui
authors.forename: S-M
authors.initials: SM
authors.lastname: Ka
authors.forename: W-M
authors.initials: WM
authors.lastname: Wu
authors.forename: Y-F
authors.initials: YF
authors.lastname: Lin
authors.forename: Y-C
authors.initials: YC
authors.lastname: Hou
authors.forename: L-C
authors.initials: LC
authors.lastname: Su
authors.forename: A
authors.initials: A
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006965:Hyperplasia; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology; D050527:Mesangial Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014178:Translocation, Genetic; D015854:Up-Regulation / Q000276:immunology
chemical_list: D001323:Autoantibodies; D020382:Interleukin-18; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger