Changes in the human peritoneal mesothelial cells during aging.
The number of older patients admitted to peritoneal dialysis (PD) programmes is growing. At the same time, there is increasing data about the role of mesothelial cells in determining the functional alteration of the peritoneum during PD. However, little is known about the functional changes accompanying the ageing process in mesothelial cells. We aimed to evaluate whether the aging process is accompanied by changes in some functional characteristic of the human peritoneal mesothelial cells (HPMC), which could account for the poor prognosis observed in old patients with PD. HPMCs were isolated from patients undergoing a nonurgent, nonseptic abdominal surgical procedure, without renal, vascular or inflammatory disease. Cytokine levels (by enzyme-linked immunosorbent assay (ELISA)), nitrates+nitrites, and cyclooxygenase (COX) activity (by a chemiluminescence assay), cytokines, COX, nitric oxide synthase (NOS), and nuclear factor (NF)-kappaB1, two messenger ribonucleic acid (mRNA) gene expressions (by reverse transcriptase (RT)-Multiplex PCR), COX, and NOS promoter gene activities, and NF-kappaB-dependent transcription (by transient transfection assays) were determined. Our data show a significant increase in cytokines, COX, and NOS activities, and mRNA expression of cytokines, COX-2, inducible nitric oxide synthase (iNOS) and precursors of NF-kappaB in HPMCs from old people. This was also the case for COX-2 and iNOS promoter gene activities and NF-kappaB-dependent transcription. There was a positive correlation between the age of the donor's cell and the proinflammatory profile of the HPMCs. Such age-dependent increase (around two-three times) is partially abolished by different antioxidant or free-radical scavengers. Thus, aging is accompanied by the presence of an inflammatory state in HPMCs, which involves the participation of different reactive oxygen species.
Nevado
J
J
Unidad de Investigación, Hospital Universitario de Getafe, Getafe, Madrid, Spain.
Vallejo
S
S
El-Assar
M
M
Peiró
C
C
Sánchez-Ferrer
C F
CF
Rodríguez-Mañas
L
L
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000235:genetics; D010529:Peritoneal Cavity / Q000166:cytology*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013859:Thiocarbamates / Q000494:pharmacology
D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D011392:Proline; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin