Spontaneous induction of nitric oxide- and prostaglandin E2-release by hypoxic astroglial cells is modulated by interleukin 1 beta.
The effect of 0, 30, 60, 120, 240, 360 min hypoxia on the release of NO and PGE2 was investigated in human cultured astroglial cells. Exposure of astroglial cells to hypoxic injury produced a dose-dependent increase of the nitrite (the breakdown product of NO) level in the cell supernatant. In addition, a significant activation of the inducible isoform of NO synthase was seen, demonstrating that the enhancement on NO release produced by hypoxic injury was related to an increased biosynthesis of NO-generating enzyme(s). This effect was strongly antagonised by pretreating cells with dexamethasone (20 microM). The increase in NO release by hypoxic astroglial cells was accompanied by sustained release of PGE2, which was antagonised by the cyclooxygenase inhibitor indomethacin (10 microM), and partially attenuated by L-NAME (100 microM), a nitric oxide synthase inhibitor, showing that the release of PGE2 was driven by NO. Finally, inducible NOS activity elicited by hypoxic injury, was antagonised by incubating astroglial cells with antibodies directed against type 2 receptor for IL1 beta. In conclusion, hypoxia stimulates cytokine network in astroglial cells leading to enhanced release of NO and prostanoids and this may represent a key mechanism in cerebral blood flow disturbances.
Mollace
V
V
Department of Biology, University of Rome Tor Vergata, Italy.
Muscoli
C
C
Rotiroti
D
D
Nisticó
G
G
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology*; D001254:Astrocytoma; D015687:Cell Hypoxia / Q000187:drug effects; D002474:Cell-Free System; D015232:Dinoprostone / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin