Rat area postrema microglial cells act as sensors for the toll-like receptor-4 agonist lipopolysaccharide.
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 (LPS), 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.
Wuchert
Florian
F
Institute for Veterinary-Physiology, Justus-Liebig University Giessen, Frankfurter Strasse 100, D-35392 Giessen, Germany.
Ott
Daniala
D
Murgott
Jolanta
J
Rafalzik
Sandra
S
Hitzel
Norma
N
Roth
Joachim
J
Gerstberger
Rüdiger
R
D000818:Animals; D000831:Animals, Newborn; D031608:Area Postrema / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D017628:Microglia / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium