title: Regulation of apoptosis by lethal cytokines in human mesothelial cells.
abstract: BACKGROUND
  Dysregulation of peritoneal cell death may contribute to the complications of peritoneal dialysis (PD). Chronic peritoneal dialysis and acute peritonitis are both associated with loss of mesothelial cells. In addition, acute peritonitis is characterized by sudden changes in the number of peritoneal leukocytes. However, the factors regulating peritoneal cell survival are poorly understood.
  
  
  METHODS
  Peritoneal effluent cells and mesothelial cells cultured from peritoneal dialysis patients were studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry were used to assess the expression of FasL and Fas mRNA and protein. Western blot was used to assess FasL and tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). RT-PCR was used to study TRAIL and TRAIL receptor mRNA. Apoptosis was quantified by flow cytometry of DNA content and confirmed by morphology.
  
  
  RESULTS
  Apoptotic cells, including apoptotic mesothelial cells, were present in the peritoneal effluent of stable peritoneal dialysis patients and patients with bacterial peritonitis. The lethal cytokines FasL and TRAIL were expressed by peritoneal effluent cells, while cultured mesothelial cells expressed FasL, Fas, and TRAIL receptors. Cultured mesothelial cells were sensitive to FasL-induced apoptosis. IFNgamma increased the cell surface expression of Fas and the sensitivity of mesothelial cells to FasL-induced apoptosis. In contrast to the effect of FasL, TNFalpha and TRAIL did not induce apoptosis in human mesothelial cells from peritoneal dialysis patients.
  
  
  CONCLUSIONS
  Lethal cytokines, such as FasL, may contribute to peritoneal cell turnover and the loss of mesothelium in peritoneal dialysis. The role of other cytokines, such as TRAIL, remains undefined. Approaches in limiting mesothelial cell injury that interferes with apoptosis should be considered.
authors.affiliation: Grupo de estudios peritoneales de Madrid-Fundación Renal Iñigo Alvarez de Toledo/Instituto Reina Sofia de Investigaciones Nefrológicas, Madrid, Spain.
authors.forename: Marina Penélope
authors.initials: MP
authors.lastname: Catalan
authors.forename: Dolores
authors.initials: D
authors.lastname: Subirá
authors.forename: Ana
authors.initials: A
authors.lastname: Reyero
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.forename: Arturo
authors.initials: A
authors.lastname: Ortiz-Gonzalez
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D000368:Aged; D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010538:Peritonitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor