PMID- 29228365
OWN - NLM
STAT- MEDLINE
DCOM- 20190912
LR  - 20190912
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 218
IP  - 2
DP  - 2018 Jun 20
TI  - Notch4 Negatively Regulates the Inflammatory Response to Mycobacterium
      tuberculosis Infection by Inhibiting TAK1 Activation.
PG  - 312-323
LID - 10.1093/infdis/jix636 [doi]
AB  - Tuberculosis, caused by Mycobacterium tuberculosis infection, remains a global
      threat to human health, but knowledge of the molecular mechanisms underlying the 
      pathogenesis of tuberculosis is still limited. Although Notch4, a member of the
      Notch receptor family, is involved in the initiation of mammary tumors, its
      function in M. tuberculosis infection remains unclear. In this study, we found
      that Notch4-de fi cient mice were more resistant to M. tuberculosis infection,
      with a much lower bacterial burden and fewer pathological changes in the lungs.
      Notch4 inhibited M. tuberculosis-induced production of proinflammatory cytokines 
      by interaction with TAK1 and inhibition of its activation. Furthermore, we found 
      that Notch intracellular domain 4 prevented TRAF6 autoubiquitination and
      suppressed TRAF6-mediated TAK1 polyubiquitination. Finally, Notch inhibitors made
      mice more resistant to M. tuberculosis infection. These results suggest that
      Notch4 is a negative regulator of M. tuberculosis-induced inflammatory response, 
      and treatment with a Notch inhibitor could serve as a new therapeutic strategy
      for tuberculosis.
FAU - Zheng, Ruijuan
AU  - Zheng R
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
FAU - Liu, Haipeng
AU  - Liu H
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
FAU - Zhou, Yilong
AU  - Zhou Y
AD  - Department of Microbiology and Immunology, Tongji University School of Medicine, 
      Shanghai, China.
FAU - Yan, Dapeng
AU  - Yan D
AD  - Department of Immunology, School of Basic Medical Sciences, Fudan University,
      Shanghai, China.
AD  - Key Laboratory of Medical Molecular Virology, Ministries of Education and Health,
      School of Basic Medical Sciences, Fudan University, Shanghai, China.
FAU - Chen, Jianxia
AU  - Chen J
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
FAU - Ma, Dapeng
AU  - Ma D
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
FAU - Feng, Yonghong
AU  - Feng Y
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
FAU - Qin, Lianhua
AU  - Qin L
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
FAU - Liu, Feng
AU  - Liu F
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
FAU - Huang, Xiaochen
AU  - Huang X
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
FAU - Wang, Jie
AU  - Wang J
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
FAU - Ge, Baoxue
AU  - Ge B
AD  - Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji
      University School of Medicine, Shanghai, China.
AD  - Department of Microbiology and Immunology, Tongji University School of Medicine, 
      Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Cytokines)
RN  - 0 (Receptor, Notch4)
RN  - 0 (TNF Receptor-Associated Factor 6)
RN  - 0 (TRAF6 protein, mouse)
RN  - 146991-60-8 (Notch4 protein, mouse)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP kinase kinase kinase 7)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Bacterial Load
MH  - Cytokines/analysis
MH  - Disease Models, Animal
MH  - Female
MH  - *Gene Expression Regulation
MH  - HEK293 Cells
MH  - Humans
MH  - Inflammation/pathology
MH  - Lung/microbiology/pathology
MH  - MAP Kinase Kinase Kinases/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RAW 264.7 Cells
MH  - Receptor, Notch4/deficiency/*metabolism
MH  - TNF Receptor-Associated Factor 6/metabolism
MH  - Tuberculosis, Pulmonary/microbiology/*pathology
EDAT- 2017/12/12 06:00
MHDA- 2019/09/13 06:00
CRDT- 2017/12/12 06:00
PHST- 2017/06/27 00:00 [received]
PHST- 2017/12/06 00:00 [accepted]
PHST- 2017/12/12 06:00 [pubmed]
PHST- 2019/09/13 06:00 [medline]
PHST- 2017/12/12 06:00 [entrez]
AID - 4712145 [pii]
AID - 10.1093/infdis/jix636 [doi]
PST - ppublish
SO  - J Infect Dis. 2018 Jun 20;218(2):312-323. doi: 10.1093/infdis/jix636.