The concerted regulation of cPLA2, COX2, and lipocortin 1 expression by IL-1beta in A549 cells.
The pro-inflammatory effects of IL-1beta have been linked to the induction of the enzyme COX-2. We now show that in addition to increasing the expression of COX-2, IL-1beta concomittantly decreased the expression of lipocortin 1 on the surface of A549 cells. Furthermore, cytosolic PLA2 is concomittantly activated by phosphorylation-resulting in a stimulation of arachidonic acid and PGE2 release. All of these effects appear to be mediated via a common pathway of PLC and PKC activation. Activation of cPLA2 is inhibited by dexamethasone in a lipocortin 1-dependent mechanism. We present a novel hypothesis whereby the effects of IL-1beta are not only due to activation of enzymes necessary for generation of eicosanoids but also to an inhibition of mechanisms that regulate the supply of arachidonic acid.
Croxtal
J D
JD
Department of Biochemical Pharmacology, The William Harvey Research Institute, The Medical College of St. Bartholemew's Hospital, London, United Kingdom.
Newman
S P
SP
Choudhury
Q
Q
Flower
R J
RJ
D000230:Adenocarcinoma; D017305:Annexin A1 / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000032:analysis; D015153:Blotting, Western; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008175:Lung Neoplasms; D009636:Norbornanes; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D017305:Annexin A1; D000911:Antibodies, Monoclonal; D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; D016718:Arachidonic Acid; C046498:tricyclodecane-9-yl-xanthogenate; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases