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 language | English (US) |
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Pages (from-to) | 197-207 |
Number of pages | 11 |
Journal | Toxicology |
Volume | 201 |
Issue number | 1-3 |
DOIs | |
State | Published - 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.
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