title: Inhibition of NF-kappaB with Dehydroxymethylepoxyquinomicin modifies the function of human peritoneal mesothelial cells.
abstract: Peritoneal mesothelial cells exposed to bioincompatible dialysis fluids contribute to damage of the peritoneum during chronic dialysis. Inflammatory response triggered in the mesothelium leading to neovascularization and fibrosis plays an important role in that process. We studied the effects of Dehydroxymethyepoxyquinmicin (DHMEQ)-an NF-κB inhibitor on function of human peritoneal mesothelial cells (HPMC) inin vitroculture. DHMEQ studied in concentrations of 1-10 µg/ml was not toxic to HPMC. Synthesis of IL-6, MCP-1 and hyaluronan in unstimulated and stimulated with interleukin-1 (100 pg/ml) HPMC was inhibited in the presence of DHMEQ and the effect was proportional to the dose of the drug. DHMEQ (10 µg/ml) reduced in unstimulated HPMC synthesis of IL-6 (-55%), MCP-1 (-58%) and hyaluronan (-41%). Respective values for stimulated HMPC were: -63% for IL-6, -57% for MCP-1 and -67% for hyaluronan. The observed effects were due to the suppression of the expression of genes responsible for the synthesis of these molecules. DHMEQ modified the effects of the effluent dialysates from CAPD patients on the function of HMPC. Dialysate induced accelerated growth of these cells, and synthesis of collagen was inhibited in the presence of DHMEQ 10 µg/ml, by 69% and 40%, respectively. The results of our study show that DHMEQ effectively reduces inflammatory response in HMPC and prevents excessive dialysate induced proliferation and collagen synthesis in these cells. All of these effects may be beneficial during chronic peritoneal dialysis and prevents progressive dialysis-induced damage to the peritoneum.
authors.affiliation: Department of Pathophysiology, Poznań University of Medical Sciences Poznań, Poland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Sosińska
authors.affiliation: Department of Pathophysiology, Poznań University of Medical SciencesPoznań, Poland; Department of Bioethics, Poznań University of Medical SciencesPoland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Baum
authors.affiliation: Department of Pathophysiology, Poznań University of Medical Sciences Poznań, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Maćkowiak
authors.affiliation: Department of Pathophysiology, Poznań University of Medical Sciences Poznań, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Staniszewski
authors.affiliation: Department of Pathophysiology, Poznań University of Medical Sciences Poznań, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jasinski
authors.affiliation: Department of Molecular Target Medicine Screening, School of Medicine, Aichi Medical University Aichi, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.affiliation: Department of Pathophysiology, Poznań University of Medical Sciences Poznań, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bręborowicz
keywords: NF-κB inhibition; Peritoneal mesothelium; collagen; inflammation; peritoneal dialysis