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Complement Protein C3a Induces Neurotrophin Expression In Human
Microglial Cells
by Klaus Heese and Uwe Otten (Corresponding author: heese@ubaclu.unibas.ch) Department of Physiology, University of Basel, Vesalianum,
Vesalgasse 1, CH-4051 Basel, Switzerland
Inflammatory processes involving reactive microglia appear to contribute to neuronal
degeneration in the central nervous system (CNS). However, the fact that microglia release
neurotrophic factors led us to investigate the signaling mechanisms involved in
neurotrophin (NT) synthesis in a human microglial cell line. This cell line shows typical
properties of human microglia including expression of NTs such as nerve growth factor
(NGF), brain-derived neurotrophic factor (BDNF), NT-3 and NT-4/5, as well as the
NGF-receptor TrkA and the low affinity NT-receptor p75NTR . We have analyzed
various inflammatory stimuli and their potency in modulating neurotrophin expression in
microglial cells. Exposure of these cells to complement factor C3a induces NGF, BDNF and
NT-3 expression. Analyzing the mechanisms involved in this induction revealed that, in
contrast to cytokine-stimulated microglial NT expression which involves the transcription
factor NF-kappaB, other transcription factors such as AP-1 (activator protein 1) and CREB
(cAMP-response element-binding protein) contribute to complement-dependent NT synthesis in
human microglial cells. We discuss the potential of complement receptor agonists as
therapy for the treatment of neurodegenerative diseases.
PDF article (94kb)
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