Interleukin 1 amplifies receptor-mediated activation of phospholipase A2 in 3T3 fibroblasts.
Human recombinant interleukin 1 alpha (IL-1 alpha) and IL-1 beta stimulated prostaglandin E2 synthesis in 3T3 fibroblasts in a time- and concentration-dependent manner. Enhanced prostaglandin E2 synthesis after IL-1 treatment was apparent by 1 hr and continued to increase for at least 2 days. Half-maximal stimulation occurred at 0.5 pM IL-1 alpha or IL-1 beta, and both interleukins were equally effective, with maximal stimulation occurring in response to 5-10 pM IL-1. In contrast to IL-1, bradykinin stimulation of prostaglandin E2 synthesis is rapid; its effect is maximal by 5 min. In cells that had been pretreated with IL-1 for 24 hr, prostaglandin E2 synthesis in response to bradykinin was amplified more than 10-fold. IL-1 also amplified the receptor-mediated formation of prostaglandin E2 by bombesin and thrombin. The lymphokine did not affect bradykinin receptor number or affinity. IL-1 treatment induced phospholipase A2 and cyclooxygenase but not phospholipase C or prostaglandin E isomerase. It also enhanced bradykinin-stimulated GTPase activity, suggesting possible induction of the GTP-binding regulatory protein coupled to the bradykinin receptor. Thus, IL-1 enhanced receptor-mediated release of prostaglandin E2 in response to bradykinin, bombesin, and thrombin by increasing the cellular levels of phospholipase A2, cyclooxygenase, and GTP-binding regulatory protein(s).
D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone; D019204:GTP-Binding Proteins / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000096:biosynthesis; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D007375:Interleukin-1; D011458:Prostaglandins E; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D013917:Thrombin; D019204:GTP-Binding Proteins; D015232:Dinoprostone; D001839:Bombesin; D001920:Bradykinin