IL-1 beta 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 bi ological processes. In addition to its traditional role in the immune syste m, IL-1 beta plays an integral role in neural-immune and developmental proc esses in the nervous system. The pleiotropic ability of IL-1 beta may be du e to the activation of different signal transduction mechanisms in specific cell types or under certain cellular conditions. We have previously demons trated that IL-1 beta regulates healing and repair in the developing, mamma lian nervous system. In the damaged perinatal mouse brain, IL-1 beta is exp ressed in astrocytes that change from a stellate to a spindle-shaped morpho logy. The spindle-shaped astrocytes enclose the wound, separating the healt hy From damaged neural tissue. The shape change and subsequent repair proce sses are IL-1 beta activity-dependent, acting through the IL-I type 1 recep tor (IL-1R1), as co-application of the IL-1 type 1 receptor antagonist prot ein (IL-1 ra) blocks IL-1 beta induced effects. In the C6 astrocytic cell l ine. IL-1 beta induced similar shape changes and upregulated expression of the cytoskeletal protein, glial fibrillary acidic protein (GFAP). Since cyt oskeletal changes as well as specific signal transduction mechanisms, are a ssociated with increases in intracellular calcium ([Ca2+](i)), studies were carried out to determine if increases in [Ca2+](i) induced by IL-1 beta oc curred through activation of the IL-IRI in C6 cells. Cells were treated wit h 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 blo cked IL-1 beta induced increases in [Ca2+](i), indicating that IL-1 beta ac ts through the IL-1R1. Immunocytochemistry experiments showed that untreate d C6 cells nor ally express IL-1 beta, IL-ira, and IL-1R1. Thus, IL-1 syste m molecules may play a role in normal C6 astrocyte physiology. (C) 1999 ISD N. Published by Elsevier Science Ltd. All rights reserved.