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.
Braghin
Elisa
E
Department of Neurological Sciences, "Dino Ferrari" Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
Galimberti
Daniela
D
Scarpini
Elio
E
Bresolin
Nereo
N
Baron
Pierluigi
P
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