title: Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity.
abstract: Methamphetamine (Meth) abuse can lead to the breakdown of the blood-brain barrier (BBB) integrity leading to compromised CNS function. The role of Galectins in the angiogenesis process in tumor-associated endothelial cells (EC) is well established; however no data are available on the expression of Galectins in normal human brain microvascular endothelial cells and their potential role in maintaining BBB integrity. We evaluated the basal gene/protein expression levels of Galectin-1, -3 and -9 in normal primary human brain microvascular endothelial cells (BMVEC) that constitute the BBB and examined whether Meth altered Galectin expression in these cells, and if Galectin-1 treatment impacted the integrity of an in-vitro BBB. Our results showed that BMVEC expressed significantly higher levels of Galectin-1 as compared to Galectin-3 and -9. Meth treatment increased Galectin-1 expression in BMVEC. Meth induced decrease in TJ proteins ZO-1, Claudin-3 and adhesion molecule ICAM-1 was reversed by Galectin-1. Our data suggests that Galectin-1 is involved in BBB remodeling and can increase levels of TJ proteins ZO-1 and Claudin-3 and adhesion molecule ICAM-1 which helps maintain BBB tightness thus playing a neuroprotective role. Galectin-1 is thus an important regulator of immune balance from neurodegeneration to neuroprotection, which makes it an important therapeutic agent/target in the treatment of drug addiction and other neurological conditions.
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: Neil U
authors.initials: NU
authors.lastname: Parikh
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: R
authors.initials: R
authors.lastname: Aalinkeel
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Reynolds
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Nair
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Sykes
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mammen
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Schwartz
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA. Electronic address: smahajan@buffalo.edu.
authors.forename: S D
authors.initials: SD
authors.lastname: Mahajan
mesh_terms: D001921:Brain / Q000166:cytology; D050882:CREB-Binding Protein / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D042783:Endothelial Cells / Q000187:drug effects*; D037483:Galectin 1 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D062507:Claudin-5; D016207:Cytokines; D037483:Galectin 1; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D018799:Intercellular Adhesion Molecule-1; D008694:Methamphetamine; D050882:CREB-Binding Protein
keywords: Blood brain barrier; Galectin-1; Human brain microvascular endothelial cells; Methamphetamine; Oxidative stress; Proinflammatory cytokines; Tight junctions; Transendothelial electrical resistance