Intracellular Ca2+ mobilization and release into mammal CSF plays a fundamental role in the etiogenesis of fever induced by the proinflammatory cytokine interleukin-1β (IL-1β) and other pyrogens. The source and mechanism of IL-1β-induced intracellular Ca2+ mobilization was investigated using two experimental models. IL-1β (10 ng/ml) treatment of rat striatal slices preloaded with 45Ca2+ elicited a delayed (30 min) and sustained increase (125-150%) in spontaneous 45Ca2+ release that was potentiated by L-arginine (300 μM) and counteracted by N-ω-nitro-L-arginine methyl ester (L-NAME) (1 and 3 mM). The nitric oxide (NO) donors diethylamine/NO complex (sodium salt) (0.3 and 1 mM) and spermine/NO (0.1 and 0.3 mM) mimicked the effect of IL-1β on Ca2+ release. IL-1β stimulated tissue cGMP concentration, and dibutyryl cGMP enhanced Ca2+ release. The guanyl cyclase inhibitors 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one (100 μM) and 6-[phenylamino]-5,8 quinolinedione (50 μM) counteracted Ca2+ release induced by 2.5 but not 10 ng/ml IL-1β. Ruthenium red (50 μM) and, to a lesser extent, heparin (3 mg/ml) antagonized IL-1β-induced Ca2+ release, and both compounds administered together completely abolished this response. Similar results were obtained in human astrocytoma cells in which IL-1β elicited a delayed (30 min) increase in intracellular Ca2+ concentration ([Ca2+]i) (402 ± 71.2% of baseline), which was abolished by 1 mM L-NAME. These data indicate that the NO/cGMP-signaling pathway is part of the intracellular mechanism transducing IL-1β-evoked Ca2+ mobilization in glial and striatal cells and that the ryanodine and the inositol-(1,4,5)-trisphosphate-sensitive Ca2+ stores are involved.

Meini, A., Benocci, A., Frosini, M., Sgaragli, G., Pessina, G., Aldinucci, C., et al. (2000). Nitric oxide modulation of interleukin-1[beta]-evoked intracellular Ca2+ release in human astrocytoma U-373 MG cells and brain striatal slices. THE JOURNAL OF NEUROSCIENCE, 20, 8980-8986.

Nitric oxide modulation of interleukin-1[beta]-evoked intracellular Ca2+ release in human astrocytoma U-373 MG cells and brain striatal slices.

FROSINI, MARIA;ALDINUCCI, CARLO;PALMI, MITRI
2000-01-01

Abstract

Intracellular Ca2+ mobilization and release into mammal CSF plays a fundamental role in the etiogenesis of fever induced by the proinflammatory cytokine interleukin-1β (IL-1β) and other pyrogens. The source and mechanism of IL-1β-induced intracellular Ca2+ mobilization was investigated using two experimental models. IL-1β (10 ng/ml) treatment of rat striatal slices preloaded with 45Ca2+ elicited a delayed (30 min) and sustained increase (125-150%) in spontaneous 45Ca2+ release that was potentiated by L-arginine (300 μM) and counteracted by N-ω-nitro-L-arginine methyl ester (L-NAME) (1 and 3 mM). The nitric oxide (NO) donors diethylamine/NO complex (sodium salt) (0.3 and 1 mM) and spermine/NO (0.1 and 0.3 mM) mimicked the effect of IL-1β on Ca2+ release. IL-1β stimulated tissue cGMP concentration, and dibutyryl cGMP enhanced Ca2+ release. The guanyl cyclase inhibitors 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one (100 μM) and 6-[phenylamino]-5,8 quinolinedione (50 μM) counteracted Ca2+ release induced by 2.5 but not 10 ng/ml IL-1β. Ruthenium red (50 μM) and, to a lesser extent, heparin (3 mg/ml) antagonized IL-1β-induced Ca2+ release, and both compounds administered together completely abolished this response. Similar results were obtained in human astrocytoma cells in which IL-1β elicited a delayed (30 min) increase in intracellular Ca2+ concentration ([Ca2+]i) (402 ± 71.2% of baseline), which was abolished by 1 mM L-NAME. These data indicate that the NO/cGMP-signaling pathway is part of the intracellular mechanism transducing IL-1β-evoked Ca2+ mobilization in glial and striatal cells and that the ryanodine and the inositol-(1,4,5)-trisphosphate-sensitive Ca2+ stores are involved.
Meini, A., Benocci, A., Frosini, M., Sgaragli, G., Pessina, G., Aldinucci, C., et al. (2000). Nitric oxide modulation of interleukin-1[beta]-evoked intracellular Ca2+ release in human astrocytoma U-373 MG cells and brain striatal slices. THE JOURNAL OF NEUROSCIENCE, 20, 8980-8986.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/21940
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