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Publication : Interferon-γ safeguards blood-brain barrier during experimental autoimmune encephalomyelitis.

First Author  Ni C Year  2014
Journal  Am J Pathol Volume  184
Issue  12 Pages  3308-20
PubMed ID  25307346 Mgi Jnum  J:216581
Mgi Id  MGI:5609065 Doi  10.1016/j.ajpath.2014.08.019
Citation  Ni C, et al. (2014) Interferon-gamma Safeguards Blood-Brain Barrier during Experimental Autoimmune Encephalomyelitis. Am J Pathol 184(12):3308-20
abstractText  The function of blood-brain barrier is often disrupted during the progression of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the molecular mechanism of blood-brain barrier modulation during neuroinflammation remains unclear. Herein, we show that the expression of interferon-gamma (IFNgamma) receptor on endothelial cells (ECs) protected mice from the brain inflammation during EAE. IFNgamma stabilized the integrity of the cerebral endothelium and prevented the infiltration of leukocytes into the brain. Further analysis revealed that IFNgamma increased the expression of tight junction proteins zonula occludens protein 1 and occludin, as well as membranous distribution of claudin-5, in brain ECs. Silencing claudin-5 abolished the IFNgamma-mediated improvement of EC integrity. Taken together, our results show that IFNgamma, a pleiotropic proinflammatory cytokine, stabilizes blood-brain barrier integrity and, therefore, prevents brain inflammation during EAE.
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