title: Glucocorticoid signaling in myeloid cells worsens acute CNS injury and inflammation.
abstract: Glucocorticoid stress hormones (GCs) are well known for being anti-inflammatory, but some reports suggest that GCs can also augment aspects of inflammation during acute brain injury. Because the GC receptor (GR) is ubiquitously expressed throughout the brain, it is difficult to know which cell types might mediate these unusual "proinflammatory" GC actions. We examined this with cell type-specific deletion or overexpression of GR in mice experiencing seizure or ischemia. Counter to their classical anti-inflammatory actions, GR signaling in myeloid cells increased Iba-1 and CD68 staining as well as nuclear p65 levels in the injured tissue. GCs also reduced levels of occludin, claudin 5, and caveolin 1, proteins central to blood-brain-barrier integrity; these effects required GR in endothelial cells. Finally, GCs compromised neuron survival, an effect mediated by GR in myeloid and endothelial cells to a greater extent than by neuronal GR.
authors: Department of Biology, Stanford University, Stanford, California 94305-5020, USA.
authors: Shawn F
authors: SF
authors: Sorrells
authors: Javier R
authors: JR
authors: Caso
authors: Carolina D
authors: CD
authors: Munhoz
authors: Caroline K
authors: CK
authors: Hu
authors: Kevin V
authors: KV
authors: Tran
authors: Zurine D
authors: ZD
authors: Miguel
authors: Bonnie Y
authors: BY
authors: Chien
authors: Robert M
authors: RM
authors: Sapolsky
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2; D011965:Receptors, Glucocorticoid / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003345:Corticosterone; D016207:Cytokines; D049452:Green Fluorescent Proteins; D007608:Kainic Acid; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D011965:Receptors, Glucocorticoid; D000097782:NF-kappaB-Inducing Kinase; C491049:Aif1 protein, mouse; C079086:Tek protein, mouse
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