How does peripheral lipopolysaccharide induce gene expression in the brain of rats?

A. K. Singh, Y. Jiang

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

Lipopolysaccharide (LPS), the principal cell-wall component of gram-negative bacteria, is responsible for alterations in the central and peripheral tissues associated with gram-negative infections. However, the mechanism by which peripheral LPS cause central effects is not fully known. This study showed that peripheral LPS sequentially increased IL-1β and iNOS mRNA levels, NO2 level, and CRF mRNA level in the hypothalamic PVN, and corticosterone concentration in blood. Brain-endothelium, but not hypothalamic PVN samples, from LPS injected rats contained ions for LPS lipids, bound BODIPY-LPS (bLPS), and expressed TLR-4, TLP-2 and CD14 mRNAs. This suggests that (1) LPS does not cross the blood-brain barrier, and (2) brain-endothelial cells contain LPS binding sites, TLR-4, TLR-2 and CD14. Systemic LPS injection increased [14C]sucrose uptake, but did not affect [14C]dextran uptake into the brain. Thus, when injected systemically, LPS binds to its receptor and enter the endothelial cells where it increase BBB permeation in a mass-selective manner and triggers a series of signaling events leading to the development of inflammatory response in the brain.

Original languageEnglish (US)
Pages (from-to)197-207
Number of pages11
JournalToxicology
Volume201
Issue number1-3
DOIs
StatePublished - Sep 1 2004

Bibliographical note

Funding Information:
This project was partially funded by grants from the Graduate School, College of Veterinary Medicine, and Center for Food Safety of the University of Minnesota.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • BBB
  • CORT
  • GC
  • GC receptor
  • GR
  • HPP
  • I
  • IL-1β
  • INT
  • LBP
  • MALDI-TOF
  • blood-brain barrier
  • corticosterone
  • glucocorticoid
  • hypothalamic-pituitary-portal
  • inducible
  • interferon-gamma
  • interleukin-1 beta
  • lipopolysaccharide (LPS) binding protein

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