Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 204, Issue 1-2, Pages 66-74Publisher
ELSEVIER
DOI: 10.1016/j.jneuroim.2008.07.017
Keywords
Innate immunity; Pathogen-associated molecular patterns; Toll-like receptors; Circumventricular organs; Calcium imaging; Fever; Sickness behavior; Cytokines; Endotoxin-tolerance
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [GE 649/6-1]
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The area postrema (AP) represents the sensory circumventricular organ lacking endothelial blood-brain barrier function in direct vicinity to the 4th cerebral ventricle. Administration of lipopolysaccharide (LIPS), as opposed to muramyldipeptide (MDP) or fibroblast-stimulating lipopeptide-1 (FSL-1), caused fast transient rises in intracellular calcium concentrations in 10-12% of the microglial cells investigated in a primary microculture of the rat AP, with limited responses of neurons. astrocytes and oligodendrocytes. in addition, a marked release of the pro-inflammatory cytokines TNF-alpha and IL-6 was determined in LPS-treated AP microcultures. Pre-incubation of AP microcultures with LPS for 18 h suppressed LPS-induced calcium signaling and attenuated cytokine secretion. Evidently, the AP can act as a sensor for circulating LPS and has the capacity to develop endotoxin-tolerance. (C) 2008 Elsevier B.V. All rights reserved.
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