Microglial low-density lipoprotein receptor-related protein 1 modulates c-Jun N-terminal kinase activation

J Neuroimmunol. 2009 Sep 29;214(1-2):25-32. doi: 10.1016/j.jneuroim.2009.06.010. Epub 2009 Jul 7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apolipoproteins E / metabolism*
  • Blotting, Western
  • Enzyme Activation / drug effects
  • Immunohistochemistry
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Lipopolysaccharides
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Mice
  • Microglia / metabolism*
  • Nitric Oxide / biosynthesis

Substances

  • Apolipoproteins E
  • Lipopolysaccharides
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Nitric Oxide
  • JNK Mitogen-Activated Protein Kinases