Avtor/Urednik		Jurič, Damijana M; Čarman-Kržan, Marija
Naslov		Interleukin-1 beta, but not IL-1 alpha, mediates nerve growth factor secretion from rat astrocytes via type I IL-1 receptor
Tip		članek
Vir		Int J Dev Neurosci
Vol. in št.		Letnik 19, št. 7
Leto izdaje		2001
Obseg		str. 675-83
Jezik		eng
Abstrakt		In astrocytes, nerve growth factor (NGF) synthesis and secretion is stimulated by 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 of the 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 beta to cultured astrocytes was saturable and of high affinity. Mean values for the 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 characters)
Deskriptorji		INTERLEUKIN-1 RECEPTORS, INTERLEUKIN-1 NERVE GROWTH FACTORS CEREBRAL CORTEX ASTROCYTES RATS, WISTAR RADIOLIGAND ASSAY PREGNANCY, ANIMAL KINETICS SUBCELLULAR FRACTIONS IMMUNOHISTOCHEMISTRY IODINE RADIOISOTOPES ANIMALS, NEWBORN DRUG INTERACTIONS DOSE-RESPONSE RELATIONSHIP, DRUG CELL MEMBRANE BINDING, COMPETITIVE BINDING SITES