title: Galectin-1 Reduces Neuroinflammation via Modulation of Nitric Oxide-Arginase Signaling in HIV-1 Transfected Microglia: a Gold Nanoparticle-Galectin-1 "Nanoplex" a Possible Neurotherapeutic?
abstract: Galectins are a family of β-galactoside-binding lectins that are important modulators of homeostasis in the central nervous system (CNS). Galectin-1 is a pivotal regulator of microglia activation that alters the immune balance from neurodegeneration to neuroprotection and could have therapeutic relevance in HIV associated neurocognitive disorders (HAND). We have previously shown that galectin-1 treatment decreased oxidative stress in microglia and hypothesize that the mechanism underlying this phenomenon is the cross regulatory interactions between Nitric oxide (NO) and Arginase I activity in microglia. We induced microglial activation and examined the effect of galectin-1 on the expression of various M1/M2 microglial phenotypic markers. Since, TNF-α is associated with activation of microglial cells involved in pathogenesis of neurodegenerative diseases, we treated HIV transfected human microglial cell cultures (CHME-5/HIV) with TNF-α followed by treatment with galectin-1, to examine the galectin-1 mediated neuro-modulatory response. Our results show that treatment of CHME-5/HIV microglia with galectin-1 reduced TNF-α induced oxidative stress by ~40%, and also significantly reduced iNOS gene expression and NO production while correspondingly increasing arginase-1, cationic amino acid transporter (CAT-1) gene expression and arginase activity. Galectin-1 treatment results in shifting microglia polarization from M1 toward the beneficial M2 phenotype which may prevent neurodegeneration and promote neuroprotection. Thus, our data suggests that galectin-1 treatment reduces neuroinflammation in the CNS microenvironment via the modulation of the NO-arginase network in microglia and thus could play a neuroprotective role in HAND. Further, the therapeutic potential of galectin-1 could be enhanced by conjugation of galectin-1 onto gold nanoparticles (Au-NP), resulting in a nanogold-galectin-1 (Au-Gal-1) multivalent complex that will have more clinical translational efficacy than free galectin-1 by virtue of increasing the payload influx.
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Aalinkeel
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.
authors.forename: Courtney S
authors.initials: CS
authors.lastname: Mangum
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.
authors.forename: Eliane
authors.initials: E
authors.lastname: Abou-Jaoude
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Reynolds
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.
authors.forename: Maixian
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Sundquist
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.
authors.forename: Neil U
authors.initials: NU
authors.lastname: Parikh
authors.affiliation: Department of Medicine, Division of Nephrology, UB Clinical and Translational Research Center, SUNY University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA.
authors.forename: Lee D
authors.initials: LD
authors.lastname: Chaves
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.
authors.forename: Manoj J
authors.initials: MJ
authors.lastname: Mammen
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Schwartz
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA. smahajan@buffalo.edu.
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mahajan
mesh_terms: D001119:Arginase / Q000502:physiology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D037483:Galectin 1 / Q000008:administration & dosage* / Q000378:metabolism; D006046:Gold / Q000008:administration & dosage* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D037483:Galectin 1; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006046:Gold; D001119:Arginase
keywords: Arginase; Galectin-1; HIV-1 associated neurological disorders (HAND); M1/M2 phenotype; Microglia; Nitric oxide