Interleukin-3 prevents neuronal death induced by amyloid peptide.
BACKGROUND
Interleukin-3 (IL-3) is an important glycoprotein involved in regulating biological responses such as cell proliferation, survival and differentiation. Its effects are mediated via interaction with cell surface receptors. Several studies have demonstrated the expression of IL-3 in neurons and astrocytes of the hippocampus and cortices in normal mouse brain, suggesting a physiological role of IL-3 in the central nervous system. Although there is evidence indicating that IL-3 is expressed in some neuronal populations, its physiological role in these cells is poorly known.


RESULTS
In this study, we demonstrated the expression of IL-3 receptor in cortical neurons, and analyzed its influence on amyloid beta (Abeta)-treated cells. In these cells, IL-3 can activate at least three classical signalling pathways, Jak/STAT, Ras/MAP kinase and the PI 3-kinase. Viability assays indicated that IL-3 might play a neuroprotective role in cells treated with Abeta fibrils. It is of interest to note that our results suggest that cell survival induced by IL-3 required PI 3-kinase and Jak/STAT pathway activation, but not MAP kinase. In addition, IL-3 induced an increase of the anti-apoptotic protein Bcl-2.


CONCLUSIONS
Altogether these data strongly suggest that IL-3 neuroprotects neuronal cells against neurodegenerative agents like Abeta.
Zambrano
Angara
A
Instituto de Bioquímica, Facultad de Ciencias, Universidad Austral de Chile, Chile. angarazambrano@uach.cl
Otth
Carola
C
Mujica
Lorena
L
Concha
Ilona I
II
Maccioni
Ricardo B
RB
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D016229:Amyloid beta-Peptides