PMID- 17117477
OWN - NLM
STAT- MEDLINE
DCOM- 20070308
LR  - 20100924
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 210
IP  - 3
DP  - 2007 Mar
TI  - The role of MAPK in Kupffer cell toll-like receptor (TLR) 2-, TLR4-, and 
      TLR9-mediated signaling following trauma-hemorrhage.
PG  - 667-75
AB  - Severe injury deranges immune function and increases the risk of sepsis and 
      multiple organ failure. Kupffer cells play a major role in mediating 
      posttraumatic immune responses, in part via different Toll-like receptors (TLR). 
      Although mitogen-activated protein kinases (MAPK) are key elements in the TLR 
      signaling pathway, it remains unclear whether the activation of different MAPK 
      are TLR specific. Male C3H/HeN mice underwent midline laparotomy (i.e., soft 
      tissue injury), hemorrhagic shock (MAP approximately 35 mm Hg for 90 min), and 
      resuscitation. Kupffer cells were isolated 2 h thereafter, lysed and 
      immunoblotted with antibodies to p38, ERK1/2, or JNK proteins. In addition, cells 
      were preincubated with specific inhibitors of p38, ERK1/2, or JNK MAPK followed 
      by stimulation with the TLR2 agonist, zymosan; the TLR4 agonist, LPS; or the TLR9 
      agonist, CpG DNA. Cytokine (TNF-alpha, interleukin-6 (IL-6), monocyte 
      chemoattractant protein-1 (MCP-1), and KC) production was determined by 
      cytometric bead array after 24 h in culture. MAPK activity as well as TNF-alpha, 
      MCP-1, and KC production by Kupffer cells were significantly increased following 
      trauma-hemorrhage. TLR4 activation by LPS stimulation increased the levels of all 
      measured cytokines. CpG-stimulated TLR9 signaling increased TNF-alpha and IL-6 
      levels; however, it had no effect on chemokine production. Selective MAPK 
      inhibition demonstrated that chemokine production was mediated via p38 and JNK 
      MAPK activation in TLR2, -4, and -9 signaling. In contrast, TNF-alpha and IL-6 
      production was differentially regulated by MAPK depending on the TLR pathway 
      stimulated. Thus, Kupffer cell TLR signaling employs different MAPK pathways in 
      eliciting cytokine and chemokine responses following trauma-hemorrhage.
CI  - Copyright 2006 Wiley-Liss, Inc.
FAU - Thobe, Bjoern M
AU  - Thobe BM
AD  - Center for Surgical Research and Department of Surgery, University of Alabama at 
      Birmingham, Birmingham, Alabama 35294-0019, USA.
FAU - Frink, Michael
AU  - Frink M
FAU - Hildebrand, Frank
AU  - Hildebrand F
FAU - Schwacha, Martin G
AU  - Schwacha MG
FAU - Hubbard, William J
AU  - Hubbard WJ
FAU - Choudhry, Mashkoor A
AU  - Choudhry MA
FAU - Chaudry, Irshad H
AU  - Chaudry IH
LA  - eng
GR  - K02 AI049960/AI/NIAID NIH HHS/United States
GR  - R01 GM 37127/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9010-72-4 (Zymosan)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
EIN - J Cell Physiol. 2010 Nov;225(3):915
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Hemorrhage/pathology/*physiopathology
MH  - Interleukin-6/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/physiology
MH  - Kupffer Cells/pathology/*physiology
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mitogen-Activated Protein Kinase 3/physiology
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Signal Transduction/*physiology
MH  - Toll-Like Receptor 2/agonists/*physiology
MH  - Toll-Like Receptor 4/agonists/*physiology
MH  - Toll-Like Receptor 9/agonists/*physiology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Wounds and Injuries/pathology/physiopathology
MH  - Zymosan/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/physiology
EDAT- 2006/11/23 09:00
MHDA- 2007/03/09 09:00
CRDT- 2006/11/23 09:00
PHST- 2006/11/23 09:00 [pubmed]
PHST- 2007/03/09 09:00 [medline]
PHST- 2006/11/23 09:00 [entrez]
AID - 10.1002/jcp.20860 [doi]
PST - ppublish
SO  - J Cell Physiol. 2007 Mar;210(3):667-75. doi: 10.1002/jcp.20860.