Cadmium- and mercury-induced intercellular adhesion molecule-1 expression in immortalized proximal tubule cells: evidence for a role of decreased transforming growth factor-beta1.
A definitive association between the aberrant expression of cytokines and adhesion molecules in renal failure has been established. In this regard a relationship between cytokine and adhesion molecule expression is suggested but has not been shown in models of proximal tubular cell injury. To investigate the impact of acute injury on the relationship between transforming growth factor-beta 1 (TGF-beta1) and intercellular adhesion molecule-1 (ICAM-1) expression, two immortalized mouse proximal tubular epithelial cell lines were exposed to cadmium chloride or mercuric chloride (0-50 microM) for 0-8 h. ELISA and Western blot measured expression of secreted and intercellular TGF-beta1, respectively. Direct cellular ELISA or Western blot was used to assess ICAM-1 expression. Challenge with cadmium caused a greater loss of cell viability than did mercury. Interestingly, cadmium significantly decreased the amount of TGF-beta1 in the conditioned media. Although a similar trend was seen in mercury-challenged cells, no significant differences were observed. The decrease in TGF-beta1 in the culture media was not due to decreased expression of this cytokine, as intercellular levels were not affected by metal-induced injury. Significant increases in ICAM-1 protein expression were observed following cadmium and mercury challenge. The increase in ICAM-1 appears to be due to increased mRNA, as Northern blot analysis demonstrated increased message expression following a 4-h cadmium or mercury challenge. Supplementation of the culture media with exogenous TGF-beta1 decreased basal ICAM-1 expression and attenuated the cadmium-induced increase. These data suggest that metal-induced injury is associated with increased ICAM-1 expression. The mechanism of this induction may involve the decreased TGF-beta1 in the conditioned media following metal challenge. Taken together, these studies suggest a link between cytokine and adhesion molecule expression in renal injury.
Jiang
Jing
J
Department of Medical Pharmacology and Toxicology, Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA.
McCool
Brian A
BA
Parrish
Alan R
AR
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002104:Cadmium / Q000633:toxicity*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008628:Mercury / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D017077:Culture Media, Conditioned; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002104:Cadmium; D018799:Intercellular Adhesion Molecule-1; D008628:Mercury