Interleukin-1 beta mediates GDNF up-regulation upon dopaminergic injury in ventral midbrain cell cultures

We recently proposed the involvement of diffusible modulators in signalling astrocytes to increase glial cell line-derived neurotrophic factor (GDNF) expression after selective dopaminergic injury by H2O2 or L-DOPA. Here we report that interleukin-1 beta (IL-1 beta) is involved in this crosstalk between injured neurons and astrocytes. IL-1 beta was detected only in the media from challenged neuron-glia cultures. Exogenous IL-1 beta did not change GDNF protein levels in astrocyte cultures, and diminished GDNF levels in neuron-glia cultures. This decrease was not due to cell loss, as assessed by the MTT assay and immunocytochemistry. Neither H2O2 nor L-DOPA induced microglia proliferation or appeared to change its activation state. The IL-1 receptor antagonist (IL-1ra) prevented GDNF up-regulation in challenged cultures, showing that IL-1 beta is involved in the signalling between injured neurons and astrocytes. Since IL-1ra decreased the number of dopaminergic neurons in H2O2-treated cultures, we propose that IL-1 has a neuroprotective role in this system involving GDNF up-regulation. (c) 2006 Elsevier Inc. All rights reserved.