PMID- 21810259
OWN - NLM
STAT- MEDLINE
DCOM- 20120223
LR  - 20220310
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 8
DP  - 2011 Aug 2
TI  - HIV-1 Tat activates indoleamine 2,3 dioxygenase in murine organotypic hippocampal 
      slice cultures in a p38 mitogen-activated protein kinase-dependent manner.
PG  - 88
LID - 10.1186/1742-2094-8-88 [doi]
AB  - BACKGROUND: We have established that activation of the tryptophan degrading 
      enzyme indoleamine 2,3 dioxygenase (IDO) mediates the switch from 
      cytokine-induced sickness behavior to depressive-like behavior. Because human 
      immunodeficiency virus type 1 (HIV-1) Tat protein causes depressive-like behavior 
      in mice, we investigated its ability to activate IDO in organotypic hippocampal 
      slice cultures (OHSCs) derived from neonatal C57BL/6 mice. METHODS: 
      Depressive-like behavior in C57BL/6J mice was assessed by the forced swim test. 
      Expression of cytokines and IDO mRNA in OHSCs was measured by real-time RT-PCR 
      and cytokine protein was measured by enzyme-linked immunosorbent assays (ELISAs). 
      p38 MAPK phosphorylation was analyzed by western blot. RESULTS: 
      Intracerebroventricular (i.c.v.) administration of Tat (40 ng) induced 
      depressive-like behavior in the absence of sickness. Addition of Tat (40 
      ng/slice) to the medium of OHSCs induced IDO steady-state mRNA that peaked at 6 
      h. This effect was potentiated by pretreatment with IFNgamma. Tat also induced the 
      synthesis and release of TNFalpha and IL-6 protein in the supernatant of the slices 
      and increased expression of the inducible isoform of nitric oxide synthase (iNOS) 
      and the serotonin transporter (SERT). Tat had no effect on endogenous synthesis 
      of IFNgamma. To explore the mechanisms of Tat-induced IDO expression, slices were 
      pretreated with the p38 mitogen-activated protein kinase (MAPK) inhibitor SB 
      202190 for 30 min before Tat treatment. SB 202190 significantly decreased IDO 
      expression induced by Tat, and this effect was accompanied by a reduction of 
      Tat-induced expression of TNFalpha, IL-6, iNOS and SERT. CONCLUSION: These data 
      establish that Tat induces IDO expression via an IFNgamma-independent mechanism that 
      depends upon activation of p38 MAPK. Targeting IDO itself or the p38 MAPK 
      signaling pathway could provide a novel therapy for comorbid depressive disorders 
      in HIV-1-infected patients.
FAU - Fu, Xin
AU  - Fu X
AD  - Integrative Immunology and Behavior Program, Department of Animal Sciences, 
      College of ACES, University of Illinois at Urbana-Champaign, Urbana, Illinois 
      61801, USA.
FAU - Lawson, Marcus A
AU  - Lawson MA
FAU - Kelley, Keith W
AU  - Kelley KW
FAU - Dantzer, Robert
AU  - Dantzer R
LA  - eng
GR  - R01 AG 029573/AG/NIA NIH HHS/United States
GR  - R01 AG029573-04S1/AG/NIA NIH HHS/United States
GR  - R01 MH 079829/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110802
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Comorbidity
MH  - Depression/epidemiology/physiopathology
MH  - Enzyme Activation
MH  - HIV Infections/epidemiology
MH  - HIV-1/*metabolism
MH  - Hippocampus/cytology/*enzymology
MH  - Humans
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism
MH  - Infusions, Intraventricular
MH  - Interferon-gamma/metabolism
MH  - Interleukin-6/genetics/metabolism
MH  - Lipopolysaccharides/administration & dosage
MH  - MAP Kinase Signaling System/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuropsychological Tests
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/genetics/*metabolism
MH  - tat Gene Products, Human Immunodeficiency Virus/administration & 
      dosage/genetics/*metabolism
PMC - PMC3162509
EDAT- 2011/08/04 06:00
MHDA- 2012/02/24 06:00
PMCR- 2011/08/02
CRDT- 2011/08/04 06:00
PHST- 2011/04/08 00:00 [received]
PHST- 2011/08/02 00:00 [accepted]
PHST- 2011/08/04 06:00 [entrez]
PHST- 2011/08/04 06:00 [pubmed]
PHST- 2012/02/24 06:00 [medline]
PHST- 2011/08/02 00:00 [pmc-release]
AID - 1742-2094-8-88 [pii]
AID - 10.1186/1742-2094-8-88 [doi]
PST - epublish
SO  - J Neuroinflammation. 2011 Aug 2;8:88. doi: 10.1186/1742-2094-8-88.