Human glomerular mesangial IP15 cell line as a suitable model for in vitro cadmium cytotoxicity studies

• Published in: Cell biology and toxicology Vol. 23; no. 4; pp. 267 - 278
• Main Authors: L'Azou, B, Dubus, I, Ohayon-Courtès, C, Cambar, J
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01.07.2007
• Subjects: Animal Testing Alternatives; Biomarkers - metabolism; Cadmium; Cadmium Chloride - metabolism; Cadmium Chloride - toxicity; Cell Line, Transformed; Cell Membrane - drug effects; Cell Survival - drug effects; Cytoskeletal Proteins - metabolism; Cytotoxicity; Dose-Response Relationship, Drug; Environmental Pollutants - metabolism; Environmental Pollutants - toxicity; Glomerular Mesangium - drug effects; Glomerular Mesangium - metabolism; Glomerular Mesangium - pathology; Humans; Image Processing, Computer-Assisted; Inhibitory Concentration 50; Kidneys; Models, Biological; Proteins; Spectrometry; Studies; Toxicology; Ultrafiltration
• ISSN: 0742-2091; 1573-6822
• DOI: 10.1007/s10565-006-0888-0

Cadmium represents a major environmental pollutant that may induce severe damage, especially in the kidney where cadmium accumulates. While cadmium is known to severely impair renal tubular functions, glomerular structures are also potential targets. Owing to their contractile properties, glomerular mesangial cells play a major role in the control of glomerular hemodynamics and influence the ultrafiltration coefficient. Cell cultures provide alternative and fruitful models for study of in vitro toxicology. However, the use of primary human mesangial cell cultures is hampered by their limited survival span and their rapid dedifferentiation during passages. This study presents a human stable immortalized mesangial cell line, designated IP15. Cell characteristics were investigated by the detection of known mesangial markers, as well as their ability to contract in response to angiotensin II. IP15 cells were used to investigate cadmium uptake and morphological changes such as cell contraction and cytoskeleton protein expression. The IC(50) cytotoxicity index was obtained with 3.55 micromol/L using neutral red assay for 24 h. After cadmium exposure (1 micromol/L, determined as nonlethal concentration), 0.38 microg Cd/mg protein was internalized by the cells as evaluated by inductively coupled plasma optical emission spectrometry (ICP/OES). Cadmium induced a significant cell surface reduction that correlated with smooth-muscle alpha-actin disorganization. Thus, the IP15 cell line is a suitable model for study of in vitro cadmium cytotoxicity in mesangial cells and allows sufficient material to be obtained for future studies of the intracellular effects of cadmium exposure.