Biomedical subjects

Jean-Francois Cailhier

Publications and source records attributed to Jean-Francois Cailhier.

3 recordsLinked to original sources

PubMed2006

Apoptosis and glomerulonephritis.

Glomerulonephritis (GN) is a form of autoimmunity in which apoptosis may be a double-edged sword. Resolution of GN can be promoted by apoptosis of infiltrating leucocytes and excess resident glomerular cells, leading to efficient anti-inflammatory clearance by macrophages and mesangial cells. However, unscheduled apoptosis in glomerular cells, especially epithelial cells ('podocytes') may drive progression of GN to hypocellular, nonfunctional scar. Defects in clearance of apoptotic cells may also have deleterious local effects, in addition to promoting autoimmunity itself. Nevertheless, there is strong promise for novel therapies based on new knowledge of apoptosis in GN, especially in regulation of leucocyte clearance from the inflamed glomerulus.

Animals↗

PubMed2006

Nitric oxide is an important mediator of renal tubular epithelial cell death in vitro and in murine experimental hydronephrosis.

Macrophages play a pivotal role in tissue injury and fibrosis during renal inflammation. Although macrophages may induce apoptosis of renal tubular epithelial cells, the mechanisms involved are unclear. We used a microscopically quantifiable co-culture assay to dissect the cytotoxic interaction between murine bone marrow-derived macrophages and Madin-Darby canine kidney cells and primary murine renal tubular epithelial cells. The induction of tubular cell apoptosis by cytokine-activated macrophages was reduced by inhibitors of nitric oxide synthase whereas tubular cell proliferation was unaffected. Furthermore, cytokine-activated macrophages derived from mice targeted for the deletion of inducible nitric oxide synthase were noncytotoxic. We then examined the role of nitric oxide in vivo by inhibiting inducible nitric oxide synthase in the model of murine experimental hydronephrosis. l-N(6)-(1-iminoethyl)-lysine was administered in the drinking water between days 5 and 7 after ureteric obstruction. Macrophage infiltration was comparable between groups, but treatment significantly inhibited tubular cell apoptosis at day 7. Tubular cell proliferation was unaffected. Inducible nitric oxide synthase blockade also reduced interstitial cell apoptosis and increased collagen III deposition. These data indicate that nitric oxide is a key mediator of macrophage-directed tubular cell apoptosis in vitro and in vivo and also modulates tubulointerstitial fibrosis.

Animals↗

PubMed2004

Apoptosis in glomerulonephritis.

Apoptosis is of fundamental importance and plays a key role in determining the outcome of glomerulonephritis. Under ideal circumstances,apoptosis deletes infiltrating leukocytes and excess numbers of resident cells that are surplus to requirements, thereby facilitating tissue remodeling and the restoration of normal tissue architecture. Apoptosis also has a darker side, however, and may be responsible for the deletion of critically important resident glomerular cells, resulting in hypocellular scarring and loss of renal function. Recent data indicate that glomerular cell apoptosis may be manipulated to improve outcome in experimental models of renal inflammation. It is hoped that further research will provide novel therapeutic strategies for patients with inflammatory glomerulonephritis.

Apoptosis↗