TNF-alpha and IL-1alpha induce apoptosis in subconfluent rat mesangial cells. Evidence for the involvement of hydrogen peroxide and lipid peroxidation as second messengers.
Apoptosis of mesangial cells (MC) plays a role in glomerulonephritis (GN). In this study we investigated cytokine-induced apoptosis of cultured rat MC by morphological and biochemical features. TNF-alpha and IL-1alpha induced apoptosis in rat MC in a time- and concentration-dependent fashion. RT-PCR experiments revealed that MC express the TNF-receptor 1 (p60) gene constitutively. TNF-alpha as well as IL-1alpha stimulated the production of reactive oxygen species (ROS) and induced lipid peroxidation. Coincubation with catalase inhibited TNF-alpha and IL-1alpha induced apoptosis as well as lipid peroxidation. TNF-alpha, but not IL-1alpha increased the expression of c-jun. These results provide evidence that TNF-alpha and IL-1alpha induce apoptosis in rat MC with hydrogen peroxide and lipid peroxidation as second messengers. Increased c-jun expression may be a downstream intracellular signal of TNF-alpha-, but not IL-1alpha-induced apoptosis.
Böhler
T
T
Department of Internal Medicine-Nephrology, Humboldt-University, Charité, Berlin, Germany. torsten.boehler@charite.de
Waiser
J
J
Hepburn
H
H
Gaedeke
J
J
Lehmann
C
C
Hambach
P
P
Budde
K
K
Neumayer
H H
HH
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D015290:Second Messenger Systems / Q000502:physiology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D015703:Antigens, CD; D007375:Interleukin-1; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D002374:Catalase; C022616:thiazolyl blue