The main constituent of the Alzheimer amyloid plaques is the amyloid β (Aβ) peptide shown to activate glial cells in vitro. Activated glial cells are believed to contribute to neurotoxicity through production of inflammatory cytokines, such as interleukin-1 (IL-1), chemokines and neurotoxic substances. The IL-1 system has been proposed to play a role in neurodegenerative processes and can in turn induce expression of other cytokines such as IL-6. Recently, association of IL-1 and IL-6 gene polymorphism with Alzheimer's disease was reported, suggesting that these cytokines may play an important role in the development of the disease. In this study, rat primary mixed glial cells were treated with IL-1β, Aβ(1-42) or Aβ(25-35). As expected the different treatments all resulted in activation of the transcription factor NFκB observed by electrophoretic mobility shift assay. Significant increases in IL-1β and IL-6 mRNA levels, as analysed by reverse transcriptase-polymerase chain reaction (RT-PCR), were detected after the different treatments. In addition, increased secretion of IL-6 was detected by ELISA after 96 h exposure in response to IL-1β, Aβ(1-42) or Aβ(25-35). When cells were exposed to both IL-1β and Aβ(25-35) additive effects were observed. This supports that the effect of Aβ can be potentiated by concurrent exposure to inflammatory cytokines and that the IL-1 system is not necessary for Aβ effects on IL-6 expression in agreement with previous studies.

Related Articles