期刊
TOXICOLOGY
卷 201, 期 1-3, 页码 197-207出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2004.04.015
关键词
corticotropin-releasing factor; corticosteroid; lipopolysaccharide; nitric oxide; inducible nitric oxide synthase; NF kappa B; LPS binding sites
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-1beta and NOS 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 [C-14]sucrose uptake, but did not affect [C-14]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. (C) 2004 Published by Elsevier Ireland Ltd.
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