Premium
P4‐165: Characterization of microglia derived from bone marrow hematopoietic stem cells: In vitro model for amyloid‐beta toxicity and phagocytosis
Author(s) -
Magga Johanna,
Koistinaho Jari
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.732
Subject(s) - microglia , monocyte , microbiology and biotechnology , phagocytosis , bone marrow , stem cell , biology , chemistry , immunology , inflammation
calgranulins, advanced glycation endproduct (AGE)-modified proteins and amphoterin. Since Ab is one of ligands for RAGE and RAGE is transporter of Ab from blood to brain, RAGE should have a potential role for Alzheimer’s disease (AD) pathogenesis. RAGE has alternatively spliced isofom, termed soluble RAGE (sRAGE). sRAGE acts as an endogenous competitor to RAGE because they contain same ligand binding site. Methods: Transfection with MMP-9 or 2 were performed to neuroblastoma cell line.siRNA for MMP-9 was treated to the cells to repress protein expression. Gelatinase assay was performed to show MMP-9 activity. Results: we found sRAGE is generated by cellular shadding mechanism as well as alternative splicing. When intracellular calcium level was increased, sRAGE generation from full length RAGE (fRAGE) was increased. In this process, matrix metalloprotease-9 (MMP-9) is working as a shaddase to generate sRAGE in the cells. When MMP-9 was overexpressed, more sRAGE was produced. While siRNA for MMP-9 or TAPI (MMP inhibitor) were treated to the cells, sRAGE in the media was decreased dramatically. In addition, MMP-9-induced sRAGE plays a protective role for Ab-induced cytotoxicity. Conclusions: MMP-9 plays an important role to generate sRAGE in the cells and it suggests another RAGE processing pathway in the cells.