TY - JOUR
T1 - Endotoxemia-induced cytokine-mediated responses of hippocampal astrocytes transmitted by cells of the brain-immune interface
AU - Hasegawa-Ishii, Sanae
AU - Inaba, Muneo
AU - Umegaki, Hiroyuki
AU - Unno, Keiko
AU - Wakabayashi, Keiji
AU - Shimada, Atsuyoshi
N1 - Funding Information:
We thank Ms. Takako Nagano for her technical assistance. S.H.I. is a fellow supported by the Japan Society for the Promotion of Science (JSPS). This study was supported by Grants-in-Aid for Scientific Research from JSPS (Contract Grant Nos. 22790392 and 26430061 to S.H.I. and 21590458, 24650190, and 25290020 to A.S.).
Publisher Copyright:
© 2016, Nature Publishing Group. All rights reserved.
PY - 2016/5/5
Y1 - 2016/5/5
N2 - Systemic inflammation shifts the brain microenvironment towards a proinflammatory state. However, how peripheral inflammation mediates changes in the brain remains to be clarified. We aimed to identify hippocampal cells and cytokines that respond to endotoxemia. Mice were intraperitoneally injected with lipopolysaccharide (LPS) or saline, and examined 1, 4, and 24 h after injection. Tissue cytokine concentrations in the spleens and hippocampi were determined by multiplex assays. Another group of mice were studied immunohistologically. Fourteen cytokines showed an increased concentration in the spleen, and 10 showed an increase in the hippocampus after LPS injection. Cytokines increased at 4 h (CCL2, CXCL1, CXCL2, and interleukin-6) were expressed by leptomeningeal stromal cells, choroid plexus stromal cells, choroid plexus epithelial cells, and hippocampal vascular endothelial cells, all of which were located at the brain-immune interface. Receptors for these cytokines were expressed by astrocytic endfeet. Cytokines increased at 24 h (CCL11, CXCL10, and granulocyte-colony stimulating factor) were expressed by astrocytes. Cells of the brain-immune interface therefore respond to endotoxemia with cytokine signals earlier than hippocampal parenchymal cells. In the parenchyma, astrocytes play a key role in responding to signals by using endfeet located in close apposition to the interface cells via cytokine receptors.
AB - Systemic inflammation shifts the brain microenvironment towards a proinflammatory state. However, how peripheral inflammation mediates changes in the brain remains to be clarified. We aimed to identify hippocampal cells and cytokines that respond to endotoxemia. Mice were intraperitoneally injected with lipopolysaccharide (LPS) or saline, and examined 1, 4, and 24 h after injection. Tissue cytokine concentrations in the spleens and hippocampi were determined by multiplex assays. Another group of mice were studied immunohistologically. Fourteen cytokines showed an increased concentration in the spleen, and 10 showed an increase in the hippocampus after LPS injection. Cytokines increased at 4 h (CCL2, CXCL1, CXCL2, and interleukin-6) were expressed by leptomeningeal stromal cells, choroid plexus stromal cells, choroid plexus epithelial cells, and hippocampal vascular endothelial cells, all of which were located at the brain-immune interface. Receptors for these cytokines were expressed by astrocytic endfeet. Cytokines increased at 24 h (CCL11, CXCL10, and granulocyte-colony stimulating factor) were expressed by astrocytes. Cells of the brain-immune interface therefore respond to endotoxemia with cytokine signals earlier than hippocampal parenchymal cells. In the parenchyma, astrocytes play a key role in responding to signals by using endfeet located in close apposition to the interface cells via cytokine receptors.
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U2 - 10.1038/srep25457
DO - 10.1038/srep25457
M3 - Article
C2 - 27149601
AN - SCOPUS:84966713058
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 25457
ER -