Targeting epidermal fatty acid binding protein for treatment of experimental autoimmune encephalomyelitis

Enyu Rao, Puja Singh, Yan Li, Yuwen Zhang, Young-In Chi, Jill Suttles, Bing Li

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: Multiple sclerosis (MS) is an autoimmune disease in which dysregulated immune cells attack myelin in the central nervous system (CNS), leading to irreversible neuronal degeneration. Our previous studies have demonstrated that epidermal fatty acid binding protein (E-FABP), widely expressed in immune cells, in particular in dendritic cells (DCs) and T lymphocytes, fuels the overactive immune responses in the mouse model of experimental autoimmune encephalomyelitis (EAE). Methods: In the present study, we conducted an intensive computational docking analysis to identify novel E-FABP inhibitors for regulation of immune cell functions and for treatment of EAE. Results: We demonstrate that compound [2-(4-acetylphenoxy)-9,10-dimethoxy-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one; designated as EI-03] bound to the lipid binding pocket of E-FABP and enhanced the expression of peroxisome proliferator-activating receptor (PPAR) γ. Further in vitro experiments showed that EI-03 regulated DC functions by inhibition of TNFα production while promoting IL-10 secretion. Moreover, EI-03 treatment counterregulated T cell balance by decreasing effector T cell differentiation (e.g. Th17, Th1) while increasing regulatory T cell development. Most importantly, mice treated with this newly identified compound exhibited reduced clinical symptoms of EAE in mouse models. Conclusions: Taken together, we have identified a new compound which displays a potential therapeutic benefit for treatment of MS by targeting E-FABP.

Original languageEnglish (US)
Article number28
JournalBMC Immunology
Volume16
Issue number1
DOIs
StatePublished - May 12 2015

Bibliographical note

Publisher Copyright:
© 2015 Rao et al.; licensee BioMed Central.

Keywords

  • Antigen present cells
  • EAE
  • Fatty acid binding protein
  • T lymphocytes

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