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IP-10 Promotes Blood–Brain Barrier Damage by Inducing Tumor Necrosis Factor Alpha Production in Japanese Encephalitis
by
Fu, Zhen F.
, Li, Fang
, Lou, Wenjuan
, Wang, Ke
, Zhang, Nan
, Wang, Haili
, Li, Yunchuan
, She, Ruiping
, Wang, Chong
, Cao, Shengbo
, Cui, Min
, Ma, Longhuan
, Awais, Muhammad
in
Astrocytes
/ Blood-brain barrier
/ Brain
/ Brain injury
/ c-Jun protein
/ Chemokines
/ CXCR3 protein
/ Cytokines
/ Dengue fever
/ Drug development
/ Encephalitis
/ Endothelial cells
/ Females
/ Flow cytometry
/ Immunology
/ Inflammation
/ IP-10
/ IP-10 protein
/ Japanese encephalitis virus
/ Kinases
/ Microvasculature
/ Neurological diseases
/ Permeability
/ Proteins
/ Signal transduction
/ tight junction proteins
/ Transcription factors
/ tumor necrosis factor alpha
/ Tumor necrosis factor-TNF
/ Tumor necrosis factor-α
/ Viral infections
/ Viruses
/ West Nile virus
2018
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IP-10 Promotes Blood–Brain Barrier Damage by Inducing Tumor Necrosis Factor Alpha Production in Japanese Encephalitis
by
Fu, Zhen F.
, Li, Fang
, Lou, Wenjuan
, Wang, Ke
, Zhang, Nan
, Wang, Haili
, Li, Yunchuan
, She, Ruiping
, Wang, Chong
, Cao, Shengbo
, Cui, Min
, Ma, Longhuan
, Awais, Muhammad
in
Astrocytes
/ Blood-brain barrier
/ Brain
/ Brain injury
/ c-Jun protein
/ Chemokines
/ CXCR3 protein
/ Cytokines
/ Dengue fever
/ Drug development
/ Encephalitis
/ Endothelial cells
/ Females
/ Flow cytometry
/ Immunology
/ Inflammation
/ IP-10
/ IP-10 protein
/ Japanese encephalitis virus
/ Kinases
/ Microvasculature
/ Neurological diseases
/ Permeability
/ Proteins
/ Signal transduction
/ tight junction proteins
/ Transcription factors
/ tumor necrosis factor alpha
/ Tumor necrosis factor-TNF
/ Tumor necrosis factor-α
/ Viral infections
/ Viruses
/ West Nile virus
2018
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IP-10 Promotes Blood–Brain Barrier Damage by Inducing Tumor Necrosis Factor Alpha Production in Japanese Encephalitis
by
Fu, Zhen F.
, Li, Fang
, Lou, Wenjuan
, Wang, Ke
, Zhang, Nan
, Wang, Haili
, Li, Yunchuan
, She, Ruiping
, Wang, Chong
, Cao, Shengbo
, Cui, Min
, Ma, Longhuan
, Awais, Muhammad
in
Astrocytes
/ Blood-brain barrier
/ Brain
/ Brain injury
/ c-Jun protein
/ Chemokines
/ CXCR3 protein
/ Cytokines
/ Dengue fever
/ Drug development
/ Encephalitis
/ Endothelial cells
/ Females
/ Flow cytometry
/ Immunology
/ Inflammation
/ IP-10
/ IP-10 protein
/ Japanese encephalitis virus
/ Kinases
/ Microvasculature
/ Neurological diseases
/ Permeability
/ Proteins
/ Signal transduction
/ tight junction proteins
/ Transcription factors
/ tumor necrosis factor alpha
/ Tumor necrosis factor-TNF
/ Tumor necrosis factor-α
/ Viral infections
/ Viruses
/ West Nile virus
2018
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IP-10 Promotes Blood–Brain Barrier Damage by Inducing Tumor Necrosis Factor Alpha Production in Japanese Encephalitis
Journal Article
IP-10 Promotes Blood–Brain Barrier Damage by Inducing Tumor Necrosis Factor Alpha Production in Japanese Encephalitis
2018
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Overview
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.
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.
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