Title |
IP-10 Promotes Blood–Brain Barrier Damage by Inducing Tumor Necrosis Factor Alpha Production in Japanese Encephalitis
|
---|---|
Published in |
Frontiers in immunology, May 2018
|
DOI | 10.3389/fimmu.2018.01148 |
Pubmed ID | |
Authors |
Ke Wang, Haili Wang, Wenjuan Lou, Longhuan Ma, Yunchuan Li, Nan Zhang, Chong Wang, Fang Li, Muhammad Awais, Shengbo Cao, Ruiping She, Zhen F. Fu, Min Cui |
Abstract |
Japanese encephalitis is a neuropathological disorder caused by Japanese encephalitis virus (JEV), which is characterized by severe pathological neuroinflammation and damage to the blood-brain barrier (BBB). Inflammatory cytokines/chemokines can regulate the expression of tight junction (TJ) proteins and are believed to be a leading cause of BBB disruption, but the specific mechanisms remain unclear. IP-10 is the most abundant chemokine produced in the early stage of JEV infection, but its role in BBB disruption is unknown. The administration of IP-10-neutralizing antibody ameliorated the decrease in TJ proteins and restored BBB integrity in JEV-infected mice. In vitro study showed IP-10 and JEV treatment did not directly alter the permeability of the monolayers of endothelial cells. However, IP-10 treatment promoted tumor necrosis factor alpha (TNF-α) production and IP-10-neutralizing antibody significantly reduced the production of TNF-α. Thus, TNF-α could be a downstream cytokine of IP-10, which decreased TJ proteins and damaged BBB integrity. Further study indicated that JEV infection can stimulate upregulation of the IP-10 receptor CXCR3 on astrocytes, resulting in TNF-α production through the JNK-c-Jun signaling pathway. Consequently, TNF-α affected the expression and cellular distribution of TJs in brain microvascular endothelial cells and led to BBB damage during JEV infection. Regarding regulation of the BBB, the IP-10/TNF-α cytokine axis could be considered a potential target for the development of novel therapeutics in BBB-related neurological diseases. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Portugal | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 60 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 13 | 22% |
Student > Bachelor | 7 | 12% |
Researcher | 7 | 12% |
Student > Doctoral Student | 5 | 8% |
Student > Ph. D. Student | 4 | 7% |
Other | 8 | 13% |
Unknown | 16 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 13 | 22% |
Biochemistry, Genetics and Molecular Biology | 7 | 12% |
Immunology and Microbiology | 6 | 10% |
Agricultural and Biological Sciences | 5 | 8% |
Medicine and Dentistry | 4 | 7% |
Other | 5 | 8% |
Unknown | 20 | 33% |