SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation

Autor: Bo Han Ko, Hsin-Hou Chang, Jyh Cherng Ju, Young Sheng Chang, Su Hua Huang, Cheng Wen Lin
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Chemokine
Inflammasomes
medicine.disease_cause
Severe Acute Respiratory Syndrome
pulmonary inflammation
Pyrin domain
Monocytes
lcsh:Chemistry
Mice
0302 clinical medicine
Medicine
Diffuse alveolar damage
Promoter Regions
Genetic
Lung
lcsh:QH301-705.5
Spectroscopy
Coronavirus
Mice
Knockout
biology
musculoskeletal
neural
and ocular physiology
virus diseases
Inflammasome
General Medicine
respiratory system
Computer Science Applications
Up-Regulation
Severe acute respiratory syndrome-related coronavirus
SARS-CoV unique domain (SUD)
CXCL10
Bronchoalveolar Lavage Fluid
medicine.drug
macromolecular substances
Lung injury
Catalysis
CCL5
Article
Cell Line
Inorganic Chemistry
03 medical and health sciences
Viral Proteins
NLR Family
Pyrin Domain-Containing 3 Protein
CXCL10
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
business.industry
Organic Chemistry
fungi
Pneumonia
NLRP3 inflammasome
Chemokine CXCL10
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
nervous system
SARS-coronavirus
lcsh:Biology (General)
lcsh:QD1-999
Immunology
biology.protein
business
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 3179, p 3179 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 9
ISSN: 1661-6596
1422-0067
Popis: Severe acute respiratory syndrome&ndash
associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in this study. The chemokine profile analysis indicated that SARS-CoV SUD significantly up-regulated the expression of CXCL10, CCL5 and interleukin (IL)-1&beta
in human lung epithelial cells and in the lung tissues of the mice intratracheally instilled with the recombinant plasmids. Among the SUD subdomains, SUD-MC substantially activated AP-1-mediated CXCL10 expression in vitro. In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms. Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3&minus
/&minus
mouse model. This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents.
Databáze: OpenAIRE
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