How does peripheral lipopolysaccharide induce gene expression in the brain of rats?
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 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.
Department of Veterinary Diagnostic Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA. singh001@umn.edu
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D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000305:Adrenal Cortex Hormones; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D003346:Corticotropin-Releasing Hormone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat