The induction of cellular group II phospholipase A2 by cytokines and its prevention by dexamethasone.
Treatment of rat glomerular mesangial cells with interleukin-1 beta, tumor necrosis factor or forskolin resulted in the secretion of phospholipase A2 activity into the culture medium. Essentially all of this secreted phospholipase A2 activity was recognized by monoclonal antibodies elicited against rat liver mitochondrial 14 kDa group II phospholipase A2. Immunoblot analysis and gel filtration confirmed the presence of only 14 kDa phospholipase A2 in the culture supernatant. This enzyme could hardly be detected in unstimulated mesangial cells and after a lag period of 6 to 8 hours becomes detectable in both cells and culture medium. The results indicate that the increased phospholipase A2 activity upon treatment of the cells with cytokines is not due to activation of an existing cellular pool of enzyme but is caused by induced synthesis of group II phospholipase A2. Pretreatment of the cells with dexamethasone, a known inhibitor of prostaglandin synthesis, dose-dependently inhibits cytokine-induced phospholipase A2 activity. Western immunoblot analysis of cells and culture medium demonstrates that this is not due to inhibition of existing phospholipase A2 but because dexamethasone prevents the cytokine-induced synthesis of phospholipase A2 protein.
van den Bosch
H
H
Centre for Biomembranes and Lipid Enzymology, Utrecht, The Netherlands.
Schalkwijk
C
C
Pfeilschifter
J
J
Märki
F
F
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology; D007375:Interleukin-1 / Q000494:pharmacology; D010741:Phospholipases A / Q000096:biosynthesis* / Q000145:classification / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2