Transforming growth factor beta mediates increase of mature transmembrane amyloid precursor protein in microglial cells.
By using the immortalized microglial cell line BV-2, we show that the high expression of the beta A4 amyloid precursor protein (APP), its biogenesis and metabolism is modulated by TGF beta, a cytokine with immunosuppressive activity, and by the microglia-stimulating agent LPS. TGF beta induces accumulation of cellular mature APP, the putative precursor of the amyloid subunit of Alzheimer's disease. LPS leads to an increase in cellular immature, non-amyloidogenic APP and secretion of also non-amyloidogenic APP fragments. We also demonstrate a functional involvement of ECM molecules in the regulation of microglial APP expression at mRNA and protein level by TGF beta and LPS.
Mönning
U
U
Center for Molecular Biology Heidelberg, University of Heidelberg, Germany.
Sandbrink
R
R
Banati
R B
RB
Masters
C L
CL
Beyreuther
K
K
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005109:Extracellular Matrix; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta