Heat-aggregated IgG and interleukin-1-beta stimulate manganese superoxide dismutase in mesangial cells.
The response of the glomerular mesangial cell to reactive oxygen species (ROS) has been implicated in the pathogenesis of several forms of inflammatory renal disease. As a model of glomerular inflammation, we studied the effects of heat-aggregated immunoglobulin G (HAG), an experimental immune complex, and interleukin-1 (IL-1) on the expression of the antioxidant enzyme, manganese superoxide dismutase (MnSOD), in primary cultures of rat mesangial cells. Following exposure to either HAG or IL-1 beta, increased steady-state MnSOD mRNA levels were observed and an additive effect was seen following co-treatment with HAG and IL-1 beta. No change was observed in steady-state levels of copper/zinc superoxide dismutase mRNA with HAG or IL-1 beta exposure. RNA protein synthesis inhibitor experiments demonstrated that the HAG- and IL-1 beta-mediated increase in MnSOD mRNA was dependent on new transcription, but was independent of de novo protein synthesis. Our data on the induction of the MnSOD gene by immune complexes and IL-1 beta could indicate an important role for MnSOD in the cellular defense against ROS toxicity in glomerular inflammation.
Stephanz
G B
GB
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville 32610, USA.
Gwinner
W
W
Cannon
J K
JK
Tisher
C C
CC
Nick
H S
HS
D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000201:enzymology*; D006358:Hot Temperature; D007074:Immunoglobulin G / Q000737:chemistry / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008345:Manganese; D010269:Paraquat / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D007074:Immunoglobulin G; D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D008345:Manganese; D003513:Cycloheximide; D013482:Superoxide Dismutase; D010269:Paraquat