PMID- 17823123
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 44
DP  - 2007 Nov 2
TI  - Myelin basic protein-primed T cells induce neurotrophins in glial cells via 
      alphavbeta3 [corrected] integrin.
PG  - 32222-32
AB  - Increasing the level of neurotrophins within the central nervous system may have 
      therapeutic efficacy in patients with various neurological diseases. Earlier we 
      have demonstrated that myelin basic protein (MBP)-primed T cells induce the 
      expression of various proinflammatory molecules in glial cells via cell-to-cell 
      contact. Here we describe that after Th2 polarization by gemfibrozil or other 
      drugs, MBP-primed T cells induced the expression of neurotrophic molecules such 
      as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not 
      proinflammatory molecules in microglia and astroglia via cell-to-cell contact. 
      MBP-primed Th2 cells expressed alpha5 and beta3 integrins and functional blocking 
      antibodies against both alpha5 and beta3 integrins inhibited the ability of 
      MBP-primed Th2 cells to induce glial neurotrophins. On the other hand, glial 
      cells expressed PDGF-Rbeta and neutralization of this glial receptor abrogated 
      the ability of Th2 cells to induce neurotrophins in glia. Activation of glial 
      cAMP response element-binding protein (CREB) by MBP-primed Th2 cell contact and 
      inhibition of contact-mediated expression of neurotrophins by antisense knockdown 
      of glial CREB suggest that MBP-primed Th2 cell-glia contact induces the 
      expression of neurotrophins through glial activation of CREB. Accordingly, 
      blocking of either alpha5beta3 integrins on T cells or PDGF-Rbeta on glial cells 
      impaired the ability of MBP-primed Th2 cells to induce glial activation of CREB. 
      Furthermore, we demonstrate that these MBP-primed Th2 cells entered into the 
      central nervous system and increased the expression of neurotrophins in vivo in 
      the brain. This study illuminates the importance of alpha5beta3 and PDGF-Rbeta in 
      guiding the novel neurotrophic property of neuroantigen-primed T cells via 
      activation of CREB that may be of therapeutic importance in various neurological 
      disorders.
FAU - Roy, Avik
AU  - Roy A
AD  - Department of Neurological Sciences, Rush University Medical Center, Chicago, 
      Illinois 60612, USA.
FAU - Liu, Xiaojuan
AU  - Liu X
FAU - Pahan, Kalipada
AU  - Pahan K
LA  - eng
GR  - R21 NS048923-03/NS/NINDS NIH HHS/United States
GR  - R01 NS039940/NS/NINDS NIH HHS/United States
GR  - NS48923/NS/NINDS NIH HHS/United States
GR  - NS39940/NS/NINDS NIH HHS/United States
GR  - R01 NS039940-08/NS/NINDS NIH HHS/United States
GR  - R21 NS048923/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070906
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Immunologic Factors)
RN  - 0 (Integrins)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Neurotrophin 3)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
RN  - Q8X02027X3 (Gemfibrozil)
SB  - IM
EIN - J Biol Chem. 2008 Feb 8;283(6):3688
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Separation
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Female
MH  - Gemfibrozil/pharmacology
MH  - Immunologic Factors/pharmacology
MH  - Integrins/*metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Microglia/metabolism
MH  - Myelin Basic Protein/*immunology
MH  - Neuroglia/*metabolism
MH  - Neurotrophin 3/*metabolism
MH  - Receptor, Platelet-Derived Growth Factor beta/metabolism
MH  - Th2 Cells/drug effects/*immunology
PMC - PMC2637617
MID - NIHMS30244
EDAT- 2007/09/08 09:00
MHDA- 2007/12/14 09:00
PMCR- 2009/02/09
CRDT- 2007/09/08 09:00
PHST- 2007/09/08 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/09/08 09:00 [entrez]
PHST- 2009/02/09 00:00 [pmc-release]
AID - S0021-9258(20)43048-0 [pii]
AID - 10.1074/jbc.M702899200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Nov 2;282(44):32222-32. doi: 10.1074/jbc.M702899200. Epub 2007 
      Sep 6.