PMID- 25962726
OWN - NLM
STAT- MEDLINE
DCOM- 20160120
LR  - 20181113
IS  - 1471-2172 (Electronic)
IS  - 1471-2172 (Linking)
VI  - 16
DP  - 2015 May 12
TI  - Targeting epidermal fatty acid binding protein for treatment of experimental 
      autoimmune encephalomyelitis.
PG  - 28
LID - 10.1186/s12865-015-0091-2 [doi]
LID - 28
AB  - 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) gamma. Further in 
      vitro experiments showed that EI-03 regulated DC functions by inhibition of TNFalpha 
      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.
FAU - Rao, Enyu
AU  - Rao E
AD  - The Hormel Institute, University of Minnesota, 801 16th Avenue, NE, Austin, MN, 
      55912, USA. erao@hi.umn.edu.
FAU - Singh, Puja
AU  - Singh P
AD  - The Hormel Institute, University of Minnesota, 801 16th Avenue, NE, Austin, MN, 
      55912, USA. psingh@hi.umn.edu.
FAU - Li, Yan
AU  - Li Y
AD  - The Hormel Institute, University of Minnesota, 801 16th Avenue, NE, Austin, MN, 
      55912, USA. yli@hi.umn.edu.
FAU - Zhang, Yuwen
AU  - Zhang Y
AD  - The Hormel Institute, University of Minnesota, 801 16th Avenue, NE, Austin, MN, 
      55912, USA. yzhang@hi.umn.edu.
FAU - Chi, Young-In
AU  - Chi YI
AD  - The Hormel Institute, University of Minnesota, 801 16th Avenue, NE, Austin, MN, 
      55912, USA. ychi@hi.umn.edu.
FAU - Suttles, Jill
AU  - Suttles J
AD  - Department of Microbiology and Immunology, University of Louisville, 319 Abraham 
      Flexner Way, Louisville, KY, 40202, USA. jill.suttles@louisville.edu.
FAU - Li, Bing
AU  - Li B
AD  - The Hormel Institute, University of Minnesota, 801 16th Avenue, NE, Austin, MN, 
      55912, USA. bli@hi.umn.edu.
LA  - eng
GR  - R01-AI048850/AI/NIAID NIH HHS/United States
GR  - R01-CA180986-01A1/CA/NCI NIH HHS/United States
GR  - CA177679-01A1/CA/NCI NIH HHS/United States
GR  - R01 CA177679/CA/NCI NIH HHS/United States
GR  - R01 AI048850/AI/NIAID NIH HHS/United States
GR  - R01 CA180986/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150512
PL  - England
TA  - BMC Immunol
JT  - BMC immunology
JID - 100966980
RN  - 0 (Cytokines)
RN  - 0 (Fabp5 protein, mouse)
RN  - 0 (Fatty Acid-Binding Proteins)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/metabolism
MH  - Drug Evaluation, Preclinical
MH  - Encephalomyelitis, Autoimmune, Experimental/*therapy
MH  - Fatty Acid-Binding Proteins/*antagonists & inhibitors/chemistry/metabolism
MH  - Mice, Inbred C57BL
MH  - Molecular Docking Simulation
MH  - *Molecular Targeted Therapy
MH  - Neoplasm Proteins/*antagonists & inhibitors/chemistry/metabolism
PMC - PMC4427938
EDAT- 2015/05/13 06:00
MHDA- 2016/01/21 06:00
PMCR- 2015/05/12
CRDT- 2015/05/13 06:00
PHST- 2014/11/26 00:00 [received]
PHST- 2015/04/01 00:00 [accepted]
PHST- 2015/05/13 06:00 [entrez]
PHST- 2015/05/13 06:00 [pubmed]
PHST- 2016/01/21 06:00 [medline]
PHST- 2015/05/12 00:00 [pmc-release]
AID - 10.1186/s12865-015-0091-2 [pii]
AID - 91 [pii]
AID - 10.1186/s12865-015-0091-2 [doi]
PST - epublish
SO  - BMC Immunol. 2015 May 12;16:28. doi: 10.1186/s12865-015-0091-2.