title: Microglial low-density lipoprotein receptor-related protein 1 modulates c-Jun N-terminal kinase activation.
abstract: Apolipoprotein E (apoE)-induced activation of low-density lipoprotein receptor (LDL) family members reduces inflammatory responses by suppressing c-Jun N-terminal kinase (JNK) activation. We aimed to identify which specific receptor family member mediates the effect of apoE on inflammation in primary cultures of microglia. Low-density lipoprotein receptor-related protein 1 (LRP1)-deficient (LRP1-/-) microglia were derived from mice using tissue-specific loxP/Cre recombination. Using a peptide formed from the receptor-binding region of apoE (EP), we found that LRP1 mediates the effects of apoE on microglial inflammation. Microglial LRP1 was also essential for EP to suppress JNK activation induced by lipopolysaccharide.
authors: Department of Neuroscience, Georgetown University, Washington, DC 20057-1464, USA.
authors: Ana
authors: A
authors: Pocivavsek
authors: Irina
authors: I
authors: Mikhailenko
authors: Dudley K
authors: DK
authors: Strickland
authors: G William
authors: GW
authors: Rebeck
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D015153:Blotting, Western; D004789:Enzyme Activation / Q000187:drug effects; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis
chemical_list: D001057:Apolipoproteins E; D008070:Lipopolysaccharides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases