Neurobiology of Disease (Jan 2007)
Interleukin-1β mediates GDNF up-regulation upon dopaminergic injury in ventral midbrain cell cultures
Abstract
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-1β (IL-1β) is involved in this crosstalk between injured neurons and astrocytes. IL-1β was detected only in the media from challenged neuron–glia cultures. Exogenous IL-1β 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-1β 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.