IL-1β-induced cytokine expression by spinal astrocytes

01/29/2020

Andrea Gajtko¹, Erzsebet Bakk¹, Krisztina Hollo¹

¹ Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

chronic inflammatory pain. Upon peripheral inflammation, activated spinal glial cells produce cytokines and other mediators, which may contribute to central sensitization and enhanced pain states. Our current study focuses on interleukin-1β (IL-1β), which is one of the best characterized proinflammatory cytokines. Our earlier results suggest that, IL-1β is produced mostly by spinal astrocytes during inflammatory pain in the spinal dorsal horn (SDH). On the other hand, effects of IL-1β are mediated by interleukin-1 receptor type 1 (IL-1R1). we detected in our previous study that IL-1R1 is expressed by both neurons and astrocytes in the SDH. Based on our results and the related literature, IL-1β is capable to induce cell-type specific responses. Here we investigated the effect of IL-1β on spinal astrocytes. For our investigation the primary astrocyte cultures were harvested from spinal cords of C57BL/6 wild type and IL-1R1 knock-out mice. In all experiments IL-1β treatment was applied. By using cytokine array method we demonstrated significant increase in the expressional level of IL-6, GM-CSF and CCL5 cytokines upon IL-1β treatment. The Western blot and immunocytochemical results validated the substantial increase of IL-6 and GM-CSF 16 hours after IL-1β stimulus, but in case of CCL5 this change was already observed after 8 hours. Fluorescent double labeled confocal images showed that these cytokines are produced by the spinal astrocyte cultures. Our data show that IL-1β triggers a cascade of cytokines which further influence glia-glia and glia-neuron interactions.