Additive effects of amyloid beta fragment and interleukin-1beta on interleukin-6 secretion in rat primary glial cultures.
The main constituent of the Alzheimer amyloid plaques is the amyloid beta (Abeta) 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-1beta, Abeta(1-42) or Abeta(25-35). As expected the different treatments all resulted in activation of the transcription factor NFkappaB observed by electrophoretic mobility shift assay. Significant increases in IL-1beta 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-1beta, Abeta(1-42) or Abeta(25-35). When cells were exposed to both IL-1beta and Abeta(25-35) additive effects were observed. This supports that the effect of Abeta can be potentiated by concurrent exposure to inflammatory cytokines and that the IL-1 system is not necessary for Abeta effects on IL-6 expression in agreement with previous studies.
Holmlund
Linda
L
Department of Neurochemistry and Neurotoxicology, The Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Cortés Toro
Veronica
V
Iverfeldt
Kerstin
K
D000483:Alleles; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger