Microglial low-density lipoprotein receptor-related protein 1 modulates c-Jun N-terminal kinase activation.
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.
Pocivavsek
Ana
A
Department of Neuroscience, Georgetown University, Washington, DC 20057-1464, USA.
Mikhailenko
Irina
I
Strickland
Dudley K
DK
Rebeck
G William
GW
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
D001057:Apolipoproteins E; D008070:Lipopolysaccharides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases