Cerebrovascular Cyclooxygenase-1 Expression, Regulation, and Role in Hypothalamic-Pituitary-Adrenal Axis Activation by Inflammatory Stimuli Export

@article{citeulike:5950819, 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 E2 (PGE2) 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 PGE2 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 {micro}g/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 PGE2 and downstream HPA response to proinflammatory challenges. 10.1523/JNEUROSCI.2373-09.2009}, author = {Garcia-Bueno, Borja and Serrats, Jordi and Sawchenko, Paul E.}, citeulike-article-id = {5950819}, citeulike-linkout-0 = {http://dx.doi.org/10.1523/JNEUROSCI.2373-09.2009}, citeulike-linkout-1 = {http://www.jneurosci.org/content/29/41/12970.abstract}, citeulike-linkout-2 = {http://www.jneurosci.org/content/29/41/12970.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19828811}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19828811}, day = {14}, doi = {10.1523/JNEUROSCI.2373-09.2009}, journal = {J. Neurosci.}, keywords = {endotoxin, lps}, month = {October}, number = {41}, pages = {12970--12981}, posted-at = {2009-10-16 13:16:12}, priority = {3}, title = {Cerebrovascular Cyclooxygenase-1 Expression, Regulation, and Role in Hypothalamic-Pituitary-Adrenal Axis Activation by Inflammatory Stimuli}, url = {http://dx.doi.org/10.1523/JNEUROSCI.2373-09.2009}, volume = {29}, year = {2009} }

TY - JOUR ID - citeulike:5950819 L3 - citeulike-article-id:5950819 N2 - 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 E2 (PGE2) 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 PGE2 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 {micro}g/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 PGE2 and downstream HPA response to proinflammatory challenges. 10.1523/JNEUROSCI.2373-09.2009 IS - 41 JF - J. Neurosci. EP - 12981 TI - Cerebrovascular Cyclooxygenase-1 Expression, Regulation, and Role in Hypothalamic-Pituitary-Adrenal Axis Activation by Inflammatory Stimuli VL - 29 SP - 12970 KW - endotoxin KW - lps AU - Garcia-Bueno, Borja AU - Serrats, Jordi AU - Sawchenko, Paul PY - 2009/10/14/ UR - http://dx.doi.org/10.1523/JNEUROSCI.2373-09.2009 ER -