PMID- 21843347
OWN - NLM
STAT- MEDLINE
DCOM- 20111212
LR  - 20220318
IS  - 1423-0127 (Electronic)
IS  - 1021-7770 (Print)
IS  - 1021-7770 (Linking)
VI  - 18
IP  - 1
DP  - 2011 Aug 15
TI  - Lipopolysaccharide-induced Notch signaling activation through JNK-dependent 
      pathway regulates inflammatory response.
PG  - 56
LID - 10.1186/1423-0127-18-56 [doi]
AB  - BACKGROUND: Notch and TLR pathways were found to act cooperatively to activate 
      Notch target genes and to increase the production of TLR-induced cytokines in 
      macrophages. However, the mechanism of LPS-induced Notch activation and its role 
      in sepsis still remains unclear. METHODS: We analyzed the expression patterns of 
      Notch components in a LPS-stimulated murine macrophage cell line using real-time 
      PCR and western blotting. The role of DAPT, a gamma-secretase inhibitor that is 
      known to be a potent Notch inhibitor, in LPS-induced cytokine release and 
      experimental sepsis in mice was also explored. Student's t-test was used to 
      analyze the difference between the two groups. RESULTS: We found that Notch 
      signaling was activated after LPS stimulation. The expression of Jagged 1, a 
      Notch ligand, induced by LPS occurred in a JNK-dependent manner. In addition, 
      Notch target genes were upregulated by early Notch-independent activation 
      followed by delayed Notch-dependent activation after LPS stimulation. Disruption 
      of Notch signaling by DAPT attenuated the LPS-induced inflammatory responses, 
      including vascular endothelial growth factor (VEGF) and high-mobility group box 
      chromosomal protein 1 (HMGB1), both in vitro and in vivo and partially improved 
      experimental sepsis survival. CONCLUSIONS: These findings support the existence 
      of a synergistic effect of Notch signaling and the LPS pathway both in vitro and 
      in vivo. Therefore, in the future Notch inhibitors may be utilized as adjunctive 
      agents for the treatment of sepsis syndrome.
FAU - Tsao, Po-Nien
AU  - Tsao PN
AD  - Department of Pediatrics, National Taiwan University Hospital, National Taiwan 
      University College of Medicine, Taipei, Taiwan. tsaopn@ntu.edu.tw
FAU - Wei, Shu-Chen
AU  - Wei SC
FAU - Huang, Miao-Tzu
AU  - Huang MT
FAU - Lee, Ming-Cheng
AU  - Lee MC
FAU - Chou, Hung-Chieh
AU  - Chou HC
FAU - Chen, Chien-Yi
AU  - Chen CY
FAU - Hsieh, Wu-Shiun
AU  - Hsieh WS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110815
PL  - England
TA  - J Biomed Sci
JT  - Journal of biomedical science
JID - 9421567
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Dipeptides)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Jag1 protein, mouse)
RN  - 0 (Jagged-1 Protein)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Proteins)
RN  - 0 (N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester)
RN  - 0 (Receptors, Notch)
RN  - 0 (Serrate-Jagged Proteins)
RN  - 0 (Toll-Like Receptors)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Calcium-Binding Proteins/metabolism
MH  - Cytokines/biosynthesis
MH  - Dipeptides/pharmacology
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Jagged-1 Protein
MH  - Lipopolysaccharides
MH  - MAP Kinase Kinase 4/*metabolism
MH  - Macrophages
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Notch/antagonists & inhibitors/*metabolism
MH  - Serrate-Jagged Proteins
MH  - Signal Transduction/drug effects/*physiology
MH  - Systemic Inflammatory Response Syndrome/*metabolism
MH  - Toll-Like Receptors/*metabolism
PMC - PMC3176188
EDAT- 2011/08/17 06:00
MHDA- 2011/12/14 06:00
PMCR- 2011/08/15
CRDT- 2011/08/17 06:00
PHST- 2011/04/22 00:00 [received]
PHST- 2011/08/15 00:00 [accepted]
PHST- 2011/08/17 06:00 [entrez]
PHST- 2011/08/17 06:00 [pubmed]
PHST- 2011/12/14 06:00 [medline]
PHST- 2011/08/15 00:00 [pmc-release]
AID - 1423-0127-18-56 [pii]
AID - 10.1186/1423-0127-18-56 [doi]
PST - epublish
SO  - J Biomed Sci. 2011 Aug 15;18(1):56. doi: 10.1186/1423-0127-18-56.