PMID- 27510585
OWN - NLM
STAT- MEDLINE
DCOM- 20170718
LR  - 20181113
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 30
IP  - 4
DP  - 2016 Nov
TI  - Characterization of the Kynurenine Pathway in CD8(+) Human Primary 
      Monocyte-Derived Dendritic Cells.
PG  - 620-632
AB  - The kynurenine (KYN) pathway (KP) is a major degradative pathway of the amino 
      acid, L-tryptophan (TRP), that ultimately leads to the anabolism of the essential 
      pyridine nucleotide, nicotinamide adenine dinucleotide. TRP catabolism results in 
      the production of several important metabolites, including the major immune 
      tolerance-inducing metabolite KYN, and the neurotoxin and excitotoxin quinolinic 
      acid. Dendritic cells (DCs) have been shown to mediate immunoregulatory roles 
      that mediated by TRP catabolism. However, characterization of the KP in human DCs 
      has so far only been partly delineated. It is critical to understand which KP 
      enzymes are expressed and which KP metabolites are produced to be able to 
      understand their regulatory effects on the immune response. In this study, we 
      characterized the KP in human monocyte-derived DCs (MDDCs) in comparison with the 
      human primary macrophages using RT-PCR, high-pressure gas chromatography, mass 
      spectrometry, and immunocytochemistry. Our results show that the KP is entirely 
      expressed in human MDDC. Following activation of the KP using interferon gamma, 
      MDDCs can mediate apoptosis of T (h) cells in vitro. Understanding the molecular 
      mechanisms regulating KP metabolism in MDDCs may provide renewed insight for the 
      development of novel therapeutics aimed at modulating immunological effects and 
      peripheral tolerance.
FAU - Braidy, Nady
AU  - Braidy N
AD  - Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, 
      University of New South Wales, Sydney, Australia. n.braidy@unsw.edu.au.
FAU - Rossez, Helene
AU  - Rossez H
AD  - St Vincent's Centre for Applied Medical Research, Sydney, Australia.
FAU - Lim, Chai K
AU  - Lim CK
AD  - Neuropharmacology Group, MND and Neurodegenerative Diseases Research Centre, 
      Macquarie University, Sydney, NSW, 2109, Australia.
FAU - Jugder, Bat-Erdene
AU  - Jugder BE
AD  - School of Biotechnology and Biomolecular Sciences, University of New South Wales, 
      Sydney, Australia.
FAU - Brew, Bruce J
AU  - Brew BJ
AD  - St Vincent's Centre for Applied Medical Research, Sydney, Australia.
AD  - Department of Neurology and HIV Medicine, St Vincent's Hospital, Sydney, 
      Australia.
FAU - Guillemin, Gilles J
AU  - Guillemin GJ
AD  - Neuropharmacology Group, MND and Neurodegenerative Diseases Research Centre, 
      Macquarie University, Sydney, NSW, 2109, Australia. gilles.guillemin@mq.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160810
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (CD8 Antigens)
RN  - 0 (Immunologic Factors)
RN  - 0 (RNA, Messenger)
RN  - 343-65-7 (Kynurenine)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/cytology/drug effects/enzymology
MH  - CD8 Antigens/analysis
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chromatography, Gas
MH  - Chromatography, High Pressure Liquid
MH  - Dendritic Cells/cytology/drug effects/*enzymology
MH  - Flow Cytometry
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunologic Factors/*pharmacology
MH  - Interferon-gamma/*pharmacology
MH  - Kynurenine/antagonists & inhibitors/*metabolism
MH  - Macrophages/cytology/drug effects/enzymology
MH  - Mass Spectrometry
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
OTO - NOTNLM
OT  - Human monocyte-derived dendritic cells
OT  - Indoleamine 2,3 dioxygenase
OT  - Kynurenine pathway
OT  - Quinolinic acid
EDAT- 2016/08/12 06:00
MHDA- 2017/07/19 06:00
CRDT- 2016/08/12 06:00
PHST- 2016/04/04 00:00 [received]
PHST- 2016/07/29 00:00 [accepted]
PHST- 2016/07/06 00:00 [revised]
PHST- 2016/08/12 06:00 [pubmed]
PHST- 2017/07/19 06:00 [medline]
PHST- 2016/08/12 06:00 [entrez]
AID - 10.1007/s12640-016-9657-x [pii]
AID - 10.1007/s12640-016-9657-x [doi]
PST - ppublish
SO  - Neurotox Res. 2016 Nov;30(4):620-632. doi: 10.1007/s12640-016-9657-x. Epub 2016 
      Aug 10.