The relative contribution of constitutive and inducible cyclooxygenase activity to lipopolysaccharide-induced prostaglandin production by primary cultures of rat hypothalamic astrocytes.
In this study, we have compared the time-course effects of lipopolysaccharide (LPS) and interleukin-1beta on prostaglandin (PG) production by primary cultures of rat astrocytes. At variance with interleukin-1beta, LPS produced significant increases in PGE2 release after only 1 h of incubation, an effect unlikely to depend on new protein synthesis; the involvement of constitutive cyclooxygenase (COX-1) was therefore investigated. Experiments with acetylsalicylic acid showed that 80% of PGE2 production after 1 h of treatment with LPS is accounted for by COX-1; this figure decreases to about 30% after a 24-h treatment. The increase in PGE2 production occurring after a 24-h challenge with the endotoxin seems to involve the activation of phospholipase A2. In fact, LPS-stimulated PGE2 release was significantly reduced by a peptide from the primary sequence of lipocortin-1, peptide Ac2-26, which was previously shown to inhibit phospholipase A2 in several in vitro models.
Pistritto
G
G
Institute of Pharmacology, Catholic University Medical School, Rome, Italy.
Mancuso
C
C
Tringali
G
G
Perretti
M
M
Preziosi
P
P
Navarra
P
P
D000818:Animals; D000831:Animals, Newborn; D017305:Annexin A1 / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D017305:Annexin A1; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D001241:Aspirin