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      Endothelial-Specific Knockdown of Interleukin-1 (IL-1) Type 1 Receptor Differentially Alters CNS Responses to IL-1 Depending on Its Route of Administration

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          Abstract

          Interleukin-1 (IL-1) has been implicated as a critical mediator of neuroimmune communication. In the brain, the functional receptor for IL-1, type 1 IL-1 receptor (IL-1R1), is localized primarily to the endothelial cells. In this study, we created an endothelial-specific IL-1R1 knockdown model to test the role of endothelial IL-1R1 in mediating the effects of IL-1. Neuronal activation in the hypothalamus was measured by c- fos expression in the paraventricular nucleus and the ventromedial preoptic area. In addition, two specific sickness symptoms, febrile response and reduction of locomotor activity, were studied. Intracerebroventricular injection of IL-1 induced leukocyte infiltration into the CNS, activation of hypothalamic neurons, fever, and reduced locomotor activity in normal mice. Endothelial-specific knockdown of IL-1R1 abrogated all these responses. Intraperitoneal injection of IL-1 also induced neuronal activation in the hypothalamus, fever, and reduced locomotor activity, without inducing leukocyte infiltration into the brain. Endothelial-specific knockdown of IL-1R1 suppressed intraperitoneal IL-1-induced fever, but not the induction of c- fos in hypothalamus. When IL-1 was given intravenously, endothelial knockdown of IL-1R1 abolished intravenous IL-1-induced CNS activation and the two monitored sickness symptoms. In addition, endothelial-specific knockdown of IL-1R1 blocked the induction of cyclooxygenase-2 expression induced by all three routes of IL-1 administration. These results show that the effects of intravenous and intracerebroventricular IL-1 are mediated by endothelial IL-1R1, whereas the effects of intraperitoneal IL-1 are partially dependent on endothelial IL-1R1.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          26 September 2007
          : 27
          : 39
          : 10476-10486
          Affiliations
          [1] 1Department of Oral Biology and
          [2] 2Center for Neurobiology, Ohio State University, Columbus, Ohio 43210-1094, and
          [3] 3Department of Pharmacology and Physiology, St. Louis University, St. Louis, Missouri 63106
          Author notes
          Correspondence should be addressed to Ning Quan, 4179 Postle Hall, 305 West 12th Avenue, Columbus, OH 43210-1094. quan.14@ 123456osu.edu

          *S.C. and H.Z. contributed equally to this work.

          Article
          PMC6673171 PMC6673171 6673171 3268825
          10.1523/JNEUROSCI.3357-07.2007
          6673171
          17898219
          b03113c3-ef11-4b14-965b-f6edda005a53
          Copyright © 2007 Society for Neuroscience 0270-6474/07/2710476-11$15.00/0
          History
          : 6 October 2006
          : 8 August 2007
          : 9 August 2007
          Categories
          Articles
          Behavioral/Systems/Cognitive

          blood–brain barrier,neuroimmune,illness behavior,locomotor activity,fever,cytokine

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