A nanoconjugate Apaf-1 inhibitor protects mesothelial cells from cytokine-induced injury.

Background: Inflammation may lead to tissue injury. We have studied the modulation of inflammatory milieu-induced tissue injury, as exemplified by the mesothelium. Peritoneal dialysis is complicated by peritonitis episodes that cause loss of mesothelium.

Bcl-xL prevents peritoneal dialysis solution-induced leukocyte apoptosis.

Conventional glucose-containing peritoneal dialysis solutions (PDS) with a high glucose degradation product content accelerate leukocyte apoptosis and impair peritoneal defense. Mononuclear cells are less sensitive than neutrophils to PDS-induced apoptosis, suggesting that they may express antiapoptotic molecules. Since apoptosis induced by PDS requires Bax, we explored the role of an antiapoptotic protein of the same family, Bcl-xL, in PDS-induced apoptosis in cultured peripheral blood mononuclear cells and monocytic THP-1 cells.

3,4-Dideoxyglucosone-3-ene as a mediator of peritoneal demesothelization.

Background: The mesothelium contributes significantly to the functional, structural and homeostatic properties of the peritoneum. Bioincompatible peritoneal dialysis solutions contribute to mesothelial cell loss during chronic peritoneal dialysis. Cell death has been implicated in mesothelial cell loss, but the molecular mechanisms have not been adequately characterized.

3,4-di-deoxyglucosone-3-ene promotes leukocyte apoptosis.

Background: Heat-sterilized, single-chambered, glucose-containing peritoneal dialysis solutions promote neutrophil apoptosis and impair the peritoneal antibacterial response. It has been proposed that glucose degradation products may be responsible for this effect. However, the precise contribution of individual glucose degradation products had not been addressed.

Regulation of apoptosis by lethal cytokines in human mesothelial cells.

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.

Peritoneal dialysis retardation of progression of advanced renal failure.

Objectives: The rate of decline of residual renal function is slower in peritoneal dialysis (PD) than in hemodialysis. However, it is unclear which and whether either of the two techniques modifies the natural course of renal failure. We tested whether PD influences the natural course of the progression of chronic renal failure in humans.

Acceleration of neutrophil apoptosis by glucose-containing peritoneal dialysis solutions: role of caspases.

Commercial, glucose-containing peritoneal dialysis (PD) solutions have deleterious effects on leukocytes and mesothelial cells that contribute to an impaired peritoneal defense. However, the molecular mechanisms of these deleterious effects are poorly understood. The effect of PD solutions on neutrophil viability, the molecular mechanisms of cell death, its functional consequences, and the possibilities for pharmacologic modulation have now been studied.

Expression of endothelial nitric oxide synthase in human peritoneal tissue: regulation by Escherichia coli lipopolysaccharide.

Changes in the expression of endothelial nitric oxide synthase (eNOS) in the peritoneum could be involved in the peritoneal dysfunction associated with peritoneal inflammation. Demonstrated recently in bovine endothelial cells was the existence of cytosolic proteins that bind to the 3'-untranslated region (3'-UTR) of eNOS mRNA and could be implicated in eNOS mRNA stabilization. The present work demonstrates that eNOS protein is expressed in human endothelial and mesothelial peritoneal cells.