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Journal of Neuroimmune Pharmacology

, Volume 12, Issue 1, pp 133–151 | Cite as

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?

  • Ravikumar Aalinkeel
  • Courtney S. Mangum
  • Eliane Abou-Jaoude
  • Jessica L. Reynolds
  • Maixian Liu
  • Karin Sundquist
  • Neil U. Parikh
  • Lee D. Chaves
  • Manoj J. Mammen
  • Stanley A. Schwartz
  • Supriya D. MahajanEmail author
ORIGINAL ARTICLE

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.

Keywords

Arginase Microglia HIV-1 associated neurological disorders (HAND) M1/M2 phenotype Nitric oxide Galectin-1 

Notes

Acknowledgements

The authors who like to acknowledge the funding support from the Dr. Louis Sklarow Memorial Trust 2015-2016 (Mahajan SD) and the New York State Department of Health (DOH) funded Empire Clinical Research Investigator Program (ECRIP) (Schwartz SA). The authors are extremely grateful to Dr. Jonathan Karn, Chairman and Reinberger Professor of Molecular Biology, Case Western Reserve University, Cleveland, Ohio and Director of the CASE Center for AIDS Research for the generous donation of the CHME-5/HIV cell line.

Compliance with Ethical Standards

Conflict of Interests

Authors declare no conflict of interests.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ravikumar Aalinkeel
    • 1
  • Courtney S. Mangum
    • 1
  • Eliane Abou-Jaoude
    • 1
  • Jessica L. Reynolds
    • 1
  • Maixian Liu
    • 1
  • Karin Sundquist
    • 1
  • Neil U. Parikh
    • 1
  • Lee D. Chaves
    • 2
  • Manoj J. Mammen
    • 1
  • Stanley A. Schwartz
    • 1
  • Supriya D. Mahajan
    • 1
    Email author
  1. 1.Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB’s Clinical and Translational Research CenterState University of New York at BuffaloBuffaloUSA
  2. 2.Department of Medicine, Division of Nephrology, UB Clinical and Translational Research CenterSUNY University at BuffaloBuffaloUSA

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