Cadmium-induced renal damage and proinflammatory cytokines: possible role of IL-6 in tubular epithelial cell regeneration.
Cadmium exposure in humans and experimental animals produces renal damage characterized by degeneration and necrosis of tubular epithelial cells followed by interstitial inflammation and eventual regeneration of proximal tubular cells. Since chronic kidney diseases are often associated with the presence of inflammatory cytokines and cadmium has been reported to alter cytokine expression in monocytes and the Kupffer cells of the liver, we investigated the role of proinflammatory cytokines in cadmium-induced nephrotoxicity. Increases in TNF-alpha and IL-6 cytokine mRNA transcripts and secretion were observed in the kidney following exposure of LPS-primed mice to a total of 21 mg/kg body weight cadmium administered over a 14-week period. IL-6 was the predominant cytokine expressed and was found to be present in mesangial cells. Cadmium, in the presence of LPS, was able to induce IL-6 secretion in vitro from mouse glomerular mesangial cells. Proliferative cell nuclear antigen (PCNA) staining revealed increases in regeneration of tubular epithelial cells following cadmium exposure. Furthermore, renal tubular epithelial cells responded to IL-6 by marked proliferation. Taken together, these data suggest that cadmium-induced IL-6 secretion in the kidney may act to support the regeneration of renal tubular epithelial cells that occurs in the course of cadmium nephrotoxicity.
Kayama
F
F
Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Yoshida
T
T
Elwell
M R
MR
Luster
M I
MI
D000818:Animals; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D046508:Culture Techniques; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009929:Organ Size / Q000187:drug effects; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002104:Cadmium; D007770:L-Lactate Dehydrogenase