1. Interleukin‐1β, but not IL‐1α, mediates nerve growth factor secretion from rat astrocytes via type I IL‐1 receptor
- Author
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Marija Čarman-Kržan and Damijana Mojca Jurič
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Alpha (ethology) ,Interleukin-1 receptor ,Biology ,Binding, Competitive ,Iodine Radioisotopes ,Radioligand Assay ,Developmental Neuroscience ,Pregnancy ,Internal medicine ,Nerve Growth Factor ,medicine ,Animals ,Drug Interactions ,Secretion ,Rats, Wistar ,Beta (finance) ,Receptor ,Cerebral Cortex ,Binding Sites ,Dose-Response Relationship, Drug ,Cell Membrane ,Receptors, Interleukin-1 ,Interleukin ,Immunohistochemistry ,Rats ,Kinetics ,Cytokine ,Endocrinology ,Nerve growth factor ,Animals, Newborn ,Astrocytes ,Female ,Interleukin-1 ,Subcellular Fractions ,Developmental Biology - Abstract
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 [(125)I] 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 [(125)I] IL-1 beta binding from cultured astrocytes in a monophasic manner. Anti-IL-1RI antibody completely blocked specific [(125)I] 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. Type II IL-1R is not present on rat neonatal cortical astrocytes.
- Published
- 2001