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  • Interleukin-1[beta], but not IL-1[alpha], mediates nerve growth factor secretionfrom rat astrocytes via type I IL-1 receptor
    Jurič, Damijana Mojca ; Čarman-Kržan, Marija
    In astrocytes, nerve growth factor (NGF) synthesis and secretion is stimulatedby the cytokine interleukin-1 beta (IL-1 beta). In the present study, the role of IL-1 receptor binding sites in the ... regulation of NGF release was evaluated by determining the pharmacological properties of astroglially localized IL-1 receptors, and, by comparing the effects of both the agonists (IL-1 alpha and IL-1 beta) and the antagonist (IL-1ra)-members ofthe IL-1 family on NGF secretion from rat neonatal cortical astrocytes in primary culture. Using receptor-binding studies, binding of Š(125)IĆ IL-1 betato cultured astrocytes was saturable and of high affinity. Mean values forthe K(D) and B(max) were calculated to be 60.7+/-7.4 pM and 2.5+/-0.1 fmol mg(-1) protein, respectively. The binding was rapid and readily reversible. IL-1 receptor agonists IL-1 alpha (K(i) of 341.1 pM) and IL-1 beta (K(i) 59.9 pM), as well as the antagonist IL-1ra (K(i) 257.6 pM), displaced specific Š(125)IĆ IL-1 beta binding from cultured astrocytes in a monophasic manner. Anti-IL-1RI antibody completely blocked specific Š(125)IĆ IL-1 beta binding while anti-IL-1RII antibody had no inhibitory effect. Exposure of cultured astrocytes to IL-1 alpha and IL-1 beta revealed the functional difference between the agonists in influencing NGF release. In contrast to IL-1 beta (10 U/ml), which caused a 3-fold increase in NGF secretion compared to control cells, IL-1 alpha by itself had no stimulatory action on NGF release. The simultaneous application of IL-1 alpha and IL-1 beta elicited no additive response. IL-1ra had no effect on basal NGF release but dose-dependently inhibited the stimulatory response induced by IL-1 beta. We concluded that IL-1 beta-induced NGF secretion from cultured rat cortical astrocytes is mediated by functional type I IL-1 receptors, whereas IL-1 alpha and IL-1ra, in spite of their affinity for IL-1RI, have no effect on NGF secretion from these cells. (Abstract truncated at 2000 chara
    Vir: International Journal of Developmental Neuroscience. - ISSN 0736-5748 (Letn. 19, št. 7, 2001, str. 675-683)
    Vrsta gradiva - članek, sestavni del
    Leto - 2001
    Jezik - angleški
    COBISS.SI-ID - 14534873

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