Document Detail

TAK1 negatively regulates NF-κB and p38 MAP kinase activation in Gr-1+CD11b+ neutrophils.
MedLine Citation:
PMID:  22226633     Owner:  NLM     Status:  MEDLINE    
Stringent control of NF-κB and mitogen-activated protein kinase (MAPK) signaling is critical during innate immune responses. TGF-β activated kinase-1 (TAK1) is essential for NF-κB activation in T and B cells but has precisely the opposite activity in myeloid cells. Specific deletion of TAK1 (Map3k7(ΔM/ΔM)) led to development of splenomegaly and lymphomegaly associated with neutrophilia. Compared with wild-type cells, TAK1-deficient neutrophils enhanced the phosphorylation of the kinases IKK, p38, and JNK and the production of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) after lipopolysaccharide (LPS) stimulation. Map3k7(ΔM/ΔM) mice were significantly more susceptible to LPS-induced septic shock and produced higher amounts of IL-1β, IL-6, and TNF-α in plasma than do wild-type mice. Specific ablation of p38 rescued the phenotype and functional properties of Map3k7(ΔM/ΔM) mice. Our findings identify a previously unrecognized role of TAK1 as a negative regulator of p38 and IKK activation in a cell type-specific manner.
Adebusola Alagbala Ajibade; Qinfu Wang; Jun Cui; Jia Zou; Xiaojun Xia; Mingjun Wang; Yanzheng Tong; Wei Hui; Dou Liu; Bing Su; Helen Y Wang; Rong-Fu Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-05
Journal Detail:
Title:  Immunity     Volume:  36     ISSN:  1097-4180     ISO Abbreviation:  Immunity     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-30     Completed Date:  2012-03-19     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  9432918     Medline TA:  Immunity     Country:  United States    
Other Details:
Languages:  eng     Pagination:  43-54     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Antigens, CD11b* / metabolism
Cell Proliferation
Gene Deletion
MAP Kinase Kinase Kinases / genetics,  metabolism*
Macrophages / immunology
Mice, Knockout
Models, Immunological
NF-kappa B / metabolism*
Neutrophils / cytology,  enzymology*,  immunology
Receptors, Chemokine* / metabolism
Signal Transduction
p38 Mitogen-Activated Protein Kinases / metabolism*
Grant Support
P01 CA094237/CA/NCI NIH HHS; R01 AI063348/AI/NIAID NIH HHS; R01 CA090327/CA/NCI NIH HHS; R01 CA101795/CA/NCI NIH HHS; R01 CA116408/CA/NCI NIH HHS; R01 CA121191/CA/NCI NIH HHS; R01 DA030338/DA/NIDA NIH HHS; R01 HL070225/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Antigens, CD11b; 0/Gr-1 protein, mouse; 0/NF-kappa B; 0/Receptors, Chemokine; EC Mitogen-Activated Protein Kinases; EC Kinase Kinase Kinases; EC kinase kinase kinase 7
Erratum In:
Immunity. 2012 Jan 27;36(1):153

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