Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway▿
Autor: | Shiming Lin, Ming-Fu Chang, Chung-Liang Chien, Shin C. Chang, I-Yin Chen, Hung-Yi Wu, Wen-Chin Wei, Ting-Chun Yu |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Chemokine
viruses Immunology Enzyme-Linked Immunosorbent Assay Peptidyl-Dipeptidase A medicine.disease_cause Microbiology Cell Line Downregulation and upregulation Viral Envelope Proteins Virology medicine Humans Receptor skin and connective tissue diseases Chemokine CCL2 Coronavirus Oligonucleotide Array Sequence Analysis Membrane Glycoproteins biology Kinase Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Epithelial Cells Molecular biology respiratory tract diseases Virus-Cell Interactions Up-Regulation Severe acute respiratory syndrome-related coronavirus Insect Science Spike Glycoprotein Coronavirus biology.protein Phosphorylation Casein kinase 1 Angiotensin-Converting Enzyme 2 Signal transduction Signal Transduction |
Zdroj: | Journal of Virology |
Popis: | Severe acute respiratory syndrome coronavirus (SARS-CoV) was identified to be the causative agent of SARS with atypical pneumonia. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV. It is not clear whether ACE2 conveys signals from the cell surface to the nucleus and regulates expression of cellular genes upon SARS-CoV infection. To understand the pathogenesis of SARS-CoV, human type II pneumocyte (A549) cells were incubated with the viral spike protein or with SARS-CoV virus-like particles containing the viral spike protein to examine cytokine modulation in lung cells. Results from oligonucleotide-based microarray, real-time PCR, and enzyme-linked immunosorbent assays indicated an upregulation of the fibrosis-associated chemokine (C-C motif) ligand 2 (CCL2) by the viral spike protein and the virus-like particles. The upregulation of CCL2 by SARS-CoV spike protein was mainly mediated by extracellular signal-regulated kinase 1 and 2 (ERK1/2) and AP-1 but not the IκBα-NF-κB signaling pathway. In addition, Ras and Raf upstream of the ERK1/2 signaling pathway were involved in the upregulation of CCL2. Furthermore, ACE2 receptor was activated by casein kinase II-mediated phosphorylation in cells pretreated with the virus-like particles containing spike protein. These results indicate that SARS-CoV spike protein triggers ACE2 signaling and activates fibrosis-associated CCL2 expression through the Ras-ERK-AP-1 pathway. |
Databáze: | OpenAIRE |
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