The presence of lipocortin in human embryonic skin fibroblasts and its regulation by anti-inflammatory steroids.
Human embryonic skin fibroblasts in culture produce pro-inflammatory lipid mediators and all types of prostanoids. When these cells were treated with the anti-inflammatory steroid, dexamethasone, prostaglandin production was inhibited. This phenomenon required glucocorticoid receptor occupancy and mRNA and protein synthesis. The inhibitory effect was prevented by treating the cells with a monoclonal antibody, BF 26, raised against renocortin, a lipocortin-like protein formed in rat kidney medulla interstitial cells in culture. When the proteins present in the supernatants and the cell pellets derived from control and dexamethasone-treated cells were analyzed for their ability to inhibit phospholipase A2, four inhibitory peaks, at 45, 30, 15 kDa and one peak under 12 kDa, were found in the supernatants of control and dexamethasone-treated cells, whereas one single inhibitory peak at 15 kDa was found in the cell pellets. The antiphospholipase activity was much greater in dexamethasone-treated cells than in control cells. These results suggest that preformed lipocortin exists in human cells and that lipocortin is synthesized and released under glucocorticoid treatment.
Errasfa
M
M
Rothhut
B
B
Fradin
A
A
Billardon
C
C
Junien
J L
JL
Bure
J
J
Russo-Marie
F
F
D000021:Abortifacient Agents, Steroidal / Q000494:pharmacology; D017302:Annexins; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone; D004622:Embryo, Mammalian; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D015735:Mifepristone; D011247:Pregnancy; D011458:Prostaglandins E / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism*; D014316:Tritium
D000021:Abortifacient Agents, Steroidal; D017302:Annexins; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D004963:Estrenes; D006023:Glycoproteins; D011458:Prostaglandins E; D014316:Tritium; D003609:Dactinomycin; D016718:Arachidonic Acid; D015735:Mifepristone; D003907:Dexamethasone; D003513:Cycloheximide; D015232:Dinoprostone