Interleukin-1 beta-induced cytosolic phospholipase A2 activity and protein synthesis is blocked by dexamethasone in rat mesangial cells.
Interleukin-1 beta induces gene expression and secretion of the secretory phospholipase A2 (sPLA2) and prostaglandin E2 (PGE2) release from rat mesangial cells. We have previously shown that prolonged treatment of rat mesangial cells with interleukin-1 beta (IL-1 beta) also enhances the cytosolic phospholipase A2 (cPLA2) activity. This effect of IL-1 beta on the cPLA2 activity is inhibited by actinomycin D and cycloheximide, indicating that both transcription and translation are involved. Here, we describe that IL-1 beta increases mRNA levels and protein synthesis of cPLA2 itself. In parallel with the effect of dexamethasone on the sPLA2, this glucocorticoid inhibits the IL-1 beta-enhanced cPLA2 activity as a result of the suppression of IL-1 beta-induced cPLA2 gene expression. This report suggests that the pro-inflammatory action of interleukin-1 beta may, in part, be mediated by its effects on cPLA2 activity.
Schalkwijk
C G
CG
Centre for Biomembranes and Lipid Enzymology, Utrecht, The Netherlands.
Vervoordeldonk
M
M
Pfeilschifter
J
J
van den Bosch
H
H
D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008715:Methionine / Q000378:metabolism; D010741:Phospholipases A / Q000096:biosynthesis* / Q000302:isolation & purification; D054467:Phospholipases A2; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013462:Sulfur Radioisotopes; D014158:Transcription, Genetic / Q000187:drug effects
D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide; D008715:Methionine; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone