PMID- 22364946
OWN - NLM
STAT- MEDLINE
DCOM- 20120501
LR  - 20211021
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Print)
IS  - 0161-5890 (Linking)
VI  - 50
IP  - 4
DP  - 2012 Apr
TI  - Reduced oxidative tissue damage during endotoxemia in IRAK-1 deficient mice.
PG  - 244-52
LID - 10.1016/j.molimm.2012.01.011 [doi]
AB  - The generation of reactive oxygen species (ROS) triggered by bacterial endotoxin 
      lipopolysaccharide (LPS) plays a key role during the pathogenesis of sepsis. 
      Given the key role that the interleukin-1 receptor associated kinase-1 (IRAK-1) 
      plays in LPS-mediated Toll-like-receptor 4 (TLR4) pathway, we herein tested 
      whether deletion of IRAK-1 gene in mice may render protection from LPS-induced 
      oxidative tissue damage. In this report, we studied the levels of oxidative 
      stress in vital organs including liver, kidney, and brain from wild type (WT) and 
      IRAK-1 deficient mice injected with a lethal dose of LPS (25mg/kg), a 
      TLR4-specific agonist. We demonstrated that LPS challenge induced marked 
      elevation of lipid peroxidation and nitrite levels in the plasma and tissues of 
      WT mice, as well as elevated pro-inflammatory mediators. In contrast, IRAK-1 
      deficient mice had significantly lower lipid peroxidation and nitrite levels, as 
      well as lower levels of pro-inflammatory mediators. Mechanistically, LPS 
      triggered higher levels of iNOS activity and elevated membrane translocation of 
      p47(phox), a key component of NADPH oxidase in immune cell derived from WT mice 
      compared to IRAK-1 deficient mice. Additionally, tissues harvested from WT mice 
      injected with LPS exhibited reduced activities of anti-oxidant enzymes including 
      glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD). In 
      contrast, LPS challenge failed to reduce the activities of GPx and SOD in IRAK-1 
      deficient tissues. As a consequence, LPS caused significantly pronounced damage 
      to liver and kidney tissues in WT mice as compared to IRAK-1 deficient mice.
CI  - Copyright A(c) 2012 Elsevier Ltd. All rights reserved.
FAU - Singh, Neeraj
AU  - Singh N
AD  - Department of Biomedical Sciences & Pathobiology, Virginia Tech, Blacksburg, VA 
      24061, United States.
FAU - Li, Liwu
AU  - Li L
LA  - eng
GR  - R01 AI050089/AI/NIAID NIH HHS/United States
GR  - R01 AI064414/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120224
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
SB  - IM
MH  - Animals
MH  - Endotoxemia/genetics/*immunology/pathology
MH  - Interleukin-1 Receptor-Associated Kinases/deficiency/*immunology
MH  - Lipid Peroxidation/genetics/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oxidative Stress/genetics/*immunology
MH  - Reactive Oxygen Species/immunology
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC4440666
MID - NIHMS690775
COIS- Author disclosure statement No competing financial interests exist.
EDAT- 2012/03/01 06:00
MHDA- 2012/05/02 06:00
PMCR- 2015/05/21
CRDT- 2012/02/28 06:00
PHST- 2012/01/03 00:00 [received]
PHST- 2012/01/26 00:00 [accepted]
PHST- 2012/02/28 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2012/05/02 06:00 [medline]
PHST- 2015/05/21 00:00 [pmc-release]
AID - S0161-5890(12)00012-0 [pii]
AID - 10.1016/j.molimm.2012.01.011 [doi]
PST - ppublish
SO  - Mol Immunol. 2012 Apr;50(4):244-52. doi: 10.1016/j.molimm.2012.01.011. Epub 2012 
      Feb 24.