Dyad of CD40/CD40 ligand fosters neuroinflammation at the blood-brain barrier and is regulated via JNK signaling: implications for HIV-1 encephalitis.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Servio H RamirezYuri Persidsky

Abstract

Human immunodeficiency virus 1 (HIV-1) infection may result in activation of peripheral monocytes followed by their infiltration into the CNS, where the release of proinflammatory mediators causes neurologic disease. Previously, we detected high levels of soluble CD40 ligand (CD40L) in CSF and plasma of HIV-infected patients with cognitive impairment. We now show that CD40, a receptor for CD40L, is highly expressed in brain endothelial cells of patients affected by HIV-1 encephalitis (HIVE), suggesting an important role for the CD40/CD40L dyad in regulating blood-brain barrier (BBB) functions. This concept was further supported by in vitro experiments. Exposure of primary human brain microvascular endothelial cells (BMVECs) to CD40L upregulated the expression of adhesion molecules intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, which caused a fourfold increase in monocyte adhesion to BMVECs and stimulated migration across an in vitro BBB model. Investigations into the intracellular signaling pathways that govern these events revealed that cJUN-N-terminal kinase (JNK) is critical to CD40 activation in the BMVECs. CD40L induced activation of mixed-lineage-kinase-3 and JNK, leading to the subsequent activa...Continue Reading

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Citations

Jun 17, 2011·Expert Reviews in Molecular Medicine·Paula GrammasBradley Miller
Dec 3, 2013·Journal of Neuroinflammation·Donna C DavidsonSanjay B Maggirwar
Mar 24, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Servio H RamirezYuri Persidsky
Apr 22, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Honghong YaoShilpa Buch
Aug 20, 2014·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Larisa GofmanRaghava Potula
Mar 7, 2013·Journal of Leukocyte Biology·Servio H RamirezYuri Persidsky
Oct 18, 2012·Brain, Behavior, and Immunity·Heidemarie GastAdriano Fontana
Sep 25, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Slava RomYuri Persidsky
Jul 21, 2015·Journal of Neurochemistry·Lauren A O'DonnellGlenn F Rall
Feb 11, 2015·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Yuri PersidskyServio H Ramirez
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Jul 8, 2020·International Journal of Molecular Sciences·Slava RomYuri Persidsky
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Oct 13, 2020·Pharmacology & Therapeutics·Sandeep KumarAjay Rana
Apr 4, 2021·International Journal of Molecular Sciences·Michelle A EricksonWilliam A Banks

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