Cerebrovascular cyclooxygenase-1 expression, regulation, and role in hypothalamic-pituitary-adrenal axis activation by inflammatory stimuli. The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] Journal article | | Title | Cerebrovascular cyclooxygenase-1 expression, regulation, and role in hypothalamic-pituitary-adrenal axis activation by inflammatory stimuli. | | Author(s) | García-Bueno B, Serrats J, Sawchenko PE | | Institution | Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies and Clayton Medical Research Foundation, La Jolla, California 92037, USA. | | Source | J Neurosci 2009 Oct 14; 29(41):12970-81. | | MeSH | Adrenocorticotropic Hormone
Animals
Corticosterone
Cyclooxygenase 1
Cyclooxygenase Inhibitors
Dinoprostone
Disease Models, Animal
Gene Expression Regulation
Hypothalamo-Hypophyseal System
Immunoenzyme Techniques
Inflammation
Injections, Intraventricular
Interleukin-1beta
Lipopolysaccharides
Liposomes
Male
Mice
Mice, Knockout
Microscopy, Electron, Transmission
Pituitary-Adrenal System
Pyrazoles
RNA, Messenger
Rats
Rats, Sprague-Dawley
von Willebrand Factor
| | Abstract | Systemic injection of lipopolysaccharide (LPS) is a widely used model of immune/inflammatory challenge, which can invoke a host of CNS responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis. Inducible vascular prostaglandin E(2) (PGE(2)) synthesis by endothelial (ECs) and/or perivascular cells (PVCs) (a macrophage-derived vascular cell type) is implicated in the engagement of HPA and other CNS responses, by virtue of their capacity to express cyclooxygenase-2 (COX-2) and microsomal PGE(2) synthase-1. Evidence from genetic and pharmacologic studies also supports a role for the constitutively expressed COX-1 in inflammation-induced activation of the HPA axis, although histochemical evidence to support relevant localization(s) and regulation of COX-1 expression is lacking. The present experiments fill this void in showing that COX-1 immunoreactivity (IR) and mRNA are detectable in identified PVCs and parenchymal microglia under basal conditions and is robustly expressed in these and ECs 1-3 h after intravenous injection of LPS (2 microg/kg). Confocal and electron microscopic analyses indicate distinct cellular/subcellular localizations of COX-1-IR in the three cell types. Interestingly, COX-1 expression is enhanced in ECs of brain PVC-depleted rats, supporting an anti-inflammatory role of the latter cell type. Functional involvement of COX-1 is indicated by the observation that central, but not systemic, pretreatment with the selective COX-1 inhibitor SC-560 attenuated the early phase of LPS-induced increases in adrenocorticotropin and corticosterone secretion. These findings support an involvement of COX-1 in bidirectional interplay between ECs and PVCs in initiating vascular PGE(2) and downstream HPA response to proinflammatory challenges. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19828811 |
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