title: Dysfunction of brain pericytes in chronic neuroinflammation.
abstract: Brain pericytes are uniquely positioned within the neurovascular unit to provide support to blood brain barrier (BBB) maintenance. Neurologic conditions, such as HIV-1-associated neurocognitive disorder, are associated with BBB compromise due to chronic inflammation. Little is known about pericyte dysfunction during HIV-1 infection. We found decreased expression of pericyte markers in human brains from HIV-1-infected patients (even those on antiretroviral therapy). Using primary human brain pericytes, we assessed expression of pericyte markers (α1-integrin, α-smooth muscle actin, platelet-derived growth factor-B receptor β, CX-43) and found their downregulation after treatment with tumor necrosis factor-α (TNFα) or interleukin-1 β (IL-1β). Pericyte exposure to virus or cytokines resulted in decreased secretion of factors promoting BBB formation (angiopoietin-1, transforming growth factor-β1) and mRNA for basement membrane components. TNFα and IL-1β enhanced expression of adhesion molecules in pericytes paralleling increased monocyte adhesion to pericytes. Monocyte migration across BBB models composed of human brain endothelial cells and pericytes demonstrated a diminished rate in baseline migration compared to constructs composed only of brain endothelial cells. However, exposure to the relevant chemokine, CCL2, enhanced the magnitude of monocyte migration when compared to BBB models composed of brain endothelial cells only. These data suggest an important role of pericytes in BBB regulation in neuroinflammation.
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA yuri.persidsky@tuhs.temple.edu.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Persidsky
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hill
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Dykstra
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Malika
authors.initials: M
authors.lastname: Winfield
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Reichenbach
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Raghava
authors.initials: R
authors.lastname: Potula
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Abir
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Servio H
authors.initials: SH
authors.lastname: Ramirez
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Slava
authors.initials: S
authors.lastname: Rom
mesh_terms: D000328:Adult; D001485:Basement Membrane / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002448:Cell Adhesion; D018925:Chemokines / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000473:pathology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009443:Neuritis / Q000473:pathology*; D020286:Pericytes / Q000473:pathology*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger
keywords: HIV-1; Pericyte; blood brain barrier; monocyte; neuroinflammation