Alpha1-antichymotrypsin induces TNF-alpha production and NF-kappaB activation in the murine N9 microglial cell line.
Microglia are known to accumulate in senile plaques of Alzheimer's disease (AD) together with a set of proteins including alpha(1)-antichymotrypsin (ACT). To investigate the biological effects of the interaction between ACT and microglia, we examined cytokine production by the murine N9 microglial cell line after ACT treatment. Real-time PCR analysis and specific immunoassays demonstrate that ACT triggers mRNA expression and release of TNF-alpha by N9 microglial cells. Furthermore, we show that ACT induces a significant increase in NF-kappaB nuclear translocation. Taken together, these data demonstrate that ACT might contribute to the inflammatory mechanisms present in AD senile plaques.
Department of Neurological Sciences, "Dino Ferrari" Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
Elisa
E
Braghin
Daniela
D
Galimberti
Elio
E
Scarpini
Nereo
N
Bresolin
Pierluigi
P
Baron
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D007118:Immunoassay; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011112:Polymyxin B / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism* / Q000494:pharmacology
D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000514:alpha 1-Antichymotrypsin; D011112:Polymyxin B