IL-1β increases intracellular calcium through an IL-1 type 1 receptor mediated mechanism in C6 astrocytic cells

Interleukin-1 beta (IL-1 beta) is a cytokine that regulates a variety of biological processes. In addition to its traditional role in the immune system, IL-1 beta plays an integral role in neural-immune and developmental processes in the nervous system. The pleiotropic ability of IL-1 beta may be due to the activation of different signal transduction mechanisms in specific cell types or under certain cellular conditions. We have previously demonstrated that IL-1 beta regulates healing and repair in the developing, mammalian nervous system. In the damaged perinatal mouse brain, IL-1 beta is expressed in astrocytes that change from a stellate to a spindle-shaped morphology. The spindle-shaped astrocytes enclose the wound, separating the healthy From damaged neural tissue. The shape change and subsequent repair processes are IL-1 beta activity-dependent, acting through the IL-I type 1 receptor (IL-1R1), as co-application of the IL-1 type 1 receptor antagonist protein (IL-1 ra) blocks IL-1 beta induced effects. In the C6 astrocytic cell line. IL-1 beta induced similar shape changes and upregulated expression of the cytoskeletal protein, glial fibrillary acidic protein (GFAP). Since cytoskeletal changes as well as specific signal transduction mechanisms, are associated with increases in intracellular calcium ([Ca2+](i)), studies were carried out to determine if increases in [Ca2+](i) induced by IL-1 beta occurred through activation of the IL-IRI in C6 cells. Cells were treated with IL-IP and/or IL-1 ra, followed by measurement of relative changes in [Ca-i(2+]) using fura-2 fluorescence imaging methods. IL-1 beta increased [Ca2+](i) levels in a dose and time dependent manner. Treatment with IL-1 ra blocked IL-1 beta induced increases in [Ca2+](i), indicating that IL-1 beta acts through the IL-1R1. Immunocytochemistry experiments showed that untreated C6 cells nor ally express IL-1 beta, IL-ira, and IL-1R1. Thus, IL-1 system molecules may play a role in normal C6 astrocyte physiology. (C) 1999 ISDN. Published by Elsevier Science Ltd. All rights reserved.