Prostaglandin Synthesis of Cultured Human Peritoneal Mesothelial Cells: Effect of Cytokine Stimulation and Cyclo-oxygenase Inhibitor.
- Author:
Duk Hee KANG
- Publication Type:Original Article
- MeSH:
Epoprostenol;
Glucose;
Humans*;
Interleukin-1;
Peritoneal Dialysis;
Peritoneal Dialysis, Continuous Ambulatory;
Peritonitis;
Permeability;
Plasma;
Prognosis;
Prostaglandin-Endoperoxide Synthases*;
Ultrafiltration
- From:Korean Journal of Nephrology
1999;18(6):869-876
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Peritoneal permeability of CAPD patients generally affects the ultrafiltration volume, dialytic protein loss, plasma protein level and eventual prognosis of individual patients. However, the precise mechanisms to govern the peritoneal transport rate are poorly understood. Intraperitoneal prostaglandin(PG), synthesized by peritoneal mesothelial cell(MC), appears to play a significant role in control of peritoneal permeability. We investigated MC synthesis of PGEz and active metabolite of prostacyclin, 6-keto-PGF< by radio-immunoassay following exposure to different concentrations of D-glucose(30, 60 & 90mM/L), commercial unused dialysate(1.5% glucose Dianeal(R), Baxter) & overnight dwell dialysate for 1 to 48 hours in the absence or presence of IL-1 8 (1ng/ml) & TNF-a (1ng/rnl). We also assessed the effect of cyclooxy-genase inhibitor(1 pg/ml of indomethacin) on PG synthesis of MC. Cultured human peritoneal MC was seeded at a density of 5xl(P/well in 12-well plate. After growth arrest for 48 hours following confluency, MCs were exposed to control media(serum restricted Hams F12) or various experimental conditions. At specific time points, MC supernatants were removed, centrifuged at 12,000Xg and then stored at -70C until PG assay. Exposure of MC to serum-free Hams F12 media (5mM/L of glucose) resulted in a constitutive synthesis of PGEz and 6-keto-PGF> . Concentrations of PGEz and 6-keto- PGFr in supernatant of MC culture were not changed with time after exposure to high glucose(30, 60, 90mM/L of D-glucose) compared to control media. Exposure of MC with unused commercial peritoneal dialysate or drained dialysate for 2 hours stimulated significant releases of PGEz & 6-keto-PGF>. Stimulation with IL-l and TNF-a induced a significant increase in PGEz from 2 hours after exposure and showed a time-dependent increase up to 48 hours. Combined stimulation of drained dialysate with IL-1P and TNF-a to mimic the intraperitoneal condition of peritonitis was associated with a greater increase in PGEp and 6-keto-PGF, compared to each stimulation alone. Treatment of MC with indomethacin(1 pg/ml) inhibited cytokine-stimulated PGEz increase. In conclusion, stimulation of MC with commercial peritoneal dialysate or cytokine induced PG synthesis, indicating the possible mechanism of intraperitoneal PG to participate in an increased peritoneal perme-ability by peritoneal dialysis process itself and es- pecially during the peritonitis.