PMID- 20211185
OWN - NLM
STAT- MEDLINE
DCOM- 20101007
LR  - 20131121
IS  - 1879-0135 (Electronic)
IS  - 0020-7519 (Linking)
VI  - 40
IP  - 9
DP  - 2010 Aug 1
TI  - The IL-12p70/IL-10 interplay is differentially regulated by free heme and 
      hemozoin in murine bone-marrow-derived macrophages.
PG  - 1003-12
LID - 10.1016/j.ijpara.2010.02.007 [doi]
AB  - The outcome of malarial anemia is determined by a complex interplay between 
      pro-inflammatory and anti-inflammatory cytokines, its severity associated with 
      accumulation of hemozoin (Hz) in macrophages, elevated IL-10 responses and 
      impaired IL-12 production. Although free heme contributes to malarial anemia by 
      inducing oxidative damage of red blood cells (RBCs) and enhancing their clearance 
      by phagocytes, its impact on IL-12/IL-10 interactions has not been fully 
      characterized. Herein, the effect of hemin (HE) on IL-12 and IL-10 responses was 
      studied in murine bone marrow-derived macrophages (BMDM) and compared with 
      synthetic Hz. Our data reveal that HE induces modest inhibition of IL-12p70 
      responses to lipopolysaccharide (LPS) whereas Hz significantly impairs IL-12p70 
      responses to IFNgamma/LPS through down-regulation of IL-12p35 and p40 gene 
      expression. Although reactive oxygen species (ROS) are generated after short-term 
      exposure to HE and Hz, prolonged exposure to these iron protoporphyrins has 
      opposite effects on the cellular redox status, HE being the only compound able to 
      promote persistent ROS production. Accordingly, the inhibitory effect of HE on 
      IL-12p70 seems sustained by redox-dependent induction of IL-10 and is partially 
      controlled by the p38 mitogen-activated protein kinase (MAPK) signalling pathway. 
      Indeed, treatment with n-acetylcysteine (NAC) or with the p38 MAPK inhibitor 
      SB203580 inhibits IL-10 responses and significantly restores IL-12p70 responses 
      to IFNgamma/LPS in HE-conditioned BMDM. Our results suggest that oxidant stress 
      induced by free heme may potentially contribute to sustained production of IL-10 
      and down-regulation of IL-12 responses in malaria.
CI  - Copyright 2010 Australian Society for Parasitology Inc. Published by Elsevier 
      Ltd. All rights reserved.
FAU - Cambos, Mathieu
AU  - Cambos M
AD  - Department of Biological Sciences, Universite du Quebec a Montreal, Montreal, 
      Que., Canada.
FAU - Bazinet, Stefany
AU  - Bazinet S
FAU - Abed, Elie
AU  - Abed E
FAU - Sanchez-Dardon, Jaime
AU  - Sanchez-Dardon J
FAU - Bernard, Charlotte
AU  - Bernard C
FAU - Moreau, Robert
AU  - Moreau R
FAU - Olivier, Martin
AU  - Olivier M
FAU - Scorza, Tatiana
AU  - Scorza T
LA  - eng
PT  - Journal Article
DEP - 20100306
PL  - England
TA  - Int J Parasitol
JT  - International journal for parasitology
JID - 0314024
RN  - 0 (Hemeproteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Reactive Oxygen Species)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 39404-00-7 (hemozoin)
RN  - 42VZT0U6YR (Heme)
RN  - 743LRP9S7N (Hemin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Female
MH  - Heme/immunology/*metabolism
MH  - Hemeproteins/immunology/*metabolism
MH  - Hemin/metabolism
MH  - Interferon-gamma/immunology
MH  - Interleukin-10/*immunology/metabolism
MH  - Interleukin-12/antagonists & inhibitors/*immunology/metabolism
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Oxidation-Reduction
MH  - Protein Binding
MH  - *Protein Interaction Mapping
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2010/03/10 06:00
MHDA- 2010/10/12 06:00
CRDT- 2010/03/10 06:00
PHST- 2009/12/22 00:00 [received]
PHST- 2010/02/08 00:00 [revised]
PHST- 2010/02/09 00:00 [accepted]
PHST- 2010/03/10 06:00 [entrez]
PHST- 2010/03/10 06:00 [pubmed]
PHST- 2010/10/12 06:00 [medline]
AID - S0020-7519(10)00065-2 [pii]
AID - 10.1016/j.ijpara.2010.02.007 [doi]
PST - ppublish
SO  - Int J Parasitol. 2010 Aug 1;40(9):1003-12. doi: 10.1016/j.ijpara.2010.02.007. 
      Epub 2010 Mar 6.