Interleukin-1beta 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-1beta (IL-1beta) is involved in this crosstalk between injured neurons and astrocytes. IL-1beta was detected only in the media from challenged neuron-glia cultures. Exogenous IL-1beta 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-1beta 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.
Saavedra
Ana
A
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Baltazar
Graça
G
Duarte
Emília P
EP
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000502:physiology*; D007980:Levodopa / Q000633:toxicity; D008636:Mesencephalon / Q000166:cytology* / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects
D015259:Dopamine Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D016877:Oxidants; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D007980:Levodopa; D006861:Hydrogen Peroxide; C022616:thiazolyl blue; D004298:Dopamine