PMID- 18378686
OWN - NLM
STAT- MEDLINE
DCOM- 20080717
LR  - 20211020
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 22
DP  - 2008 May 30
TI  - CpG DNA prevents liver injury and shock-mediated death by modulating expression 
      of interleukin-1 receptor-associated kinases.
PG  - 15258-70
LID - 10.1074/jbc.M709549200 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) produced by macrophages in response to 
      CpG DNA induces severe liver injury and subsequent death of D-galactosamine 
      (D-GalN)-sensitized mice. In the present study we demonstrate that mice 
      pre-exposed to CpG DNA are resistant to liver injury and death induced by CpG 
      DNA/D-GalN. CpG DNA/D-GalN failed to induce TNF-alpha production and hepatocyte 
      apoptosis in the mice pre-exposed to CpG DNA. In addition, macrophages isolated 
      from the CpG DNA-pretreated mice showed suppressed activation of MAPKs and 
      NF-kappaB and production of TNF-alpha in response to CpG DNA, indicating that the 
      CpG DNA-mediated protection of CpG DNA/D-GalN-challenged mice is due to the 
      hyporesponsiveness of macrophages to CpG DNA. CpG DNA pretreatment in vivo 
      inhibited expression of interleukin-1 receptor-associated kinase (IRAK)-1 while 
      inducing IRAK-M expression in macrophages. Suppressed expression of IRAK-1 was 
      responsible for the macrophage hyporesponsiveness to CpG DNA. However, increased 
      expression of IRAK-M was not sufficient to render macrophages hyporesponsive to 
      CpG DNA but was required for induction of the optimal level of macrophage 
      hyporesponsiveness. Taken together, reduced expression of IRAK-1 and increased 
      expression of IRAK-M after CpG DNA pretreatment resulted in the 
      hyporesponsiveness of macrophages that leads to the protection of mice from 
      hepatic injury and death caused by CpG DNA/D-GalN.
FAU - Kim, Young-In
AU  - Kim YI
AD  - The Children's Foundation Research Center at Le Bonheur Children's Medical 
      Center, and Department of Pediatrics, University of Tennessee Health Science 
      Center, 50 N. Dunlap Street, Memphis, TN 38103, USA.
FAU - Park, Jeoung-Eun
AU  - Park JE
FAU - Martinez-Hernandez, Antonio
AU  - Martinez-Hernandez A
FAU - Yi, Ae-Kyung
AU  - Yi AK
LA  - eng
GR  - AI 053137/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080331
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7535-00-4 (Galactosamine)
RN  - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
RN  - EC 2.7.11.1 (Irak1 protein, mouse)
RN  - EC 2.7.11.1 (Irak3 protein, mouse)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Enzyme Activation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Galactosamine/agonists/*toxicity
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Interleukin-1 Receptor-Associated Kinases/*biosynthesis
MH  - Liver/*enzymology/injuries
MH  - Macrophages/*enzymology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Oligodeoxyribonucleotides/agonists/*toxicity
MH  - Shock/chemically induced/*enzymology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
PMC - PMC2397458
EDAT- 2008/04/02 09:00
MHDA- 2008/07/18 09:00
PMCR- 2009/05/30
CRDT- 2008/04/02 09:00
PHST- 2008/04/02 09:00 [pubmed]
PHST- 2008/07/18 09:00 [medline]
PHST- 2008/04/02 09:00 [entrez]
PHST- 2009/05/30 00:00 [pmc-release]
AID - S0021-9258(20)71549-8 [pii]
AID - 15258 [pii]
AID - 10.1074/jbc.M709549200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 May 30;283(22):15258-70. doi: 10.1074/jbc.M709549200. Epub 2008 
      Mar 31.