SARS coronavirus spike protein-induced innate immune response occurs via activation of the NF-κB pathway in human monocyte macrophages in vitro
Identifieur interne : 002A28 ( Main/Exploration ); précédent : 002A27; suivant : 002A29SARS coronavirus spike protein-induced innate immune response occurs via activation of the NF-κB pathway in human monocyte macrophages in vitro
Auteurs : Susan F. Dosch [États-Unis] ; Supriya D. Mahajan [États-Unis] ; Arlene R. Collins [États-Unis]Source :
- Virus Research [ 0168-1702 ] ; 2009.
Descripteurs français
- KwdFr :
- Cellules cultivées, Expression des gènes, Facteur de transcription RelA (génétique), Facteur de transcription RelA (immunologie), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (immunologie), Humains, Interleukine-6 (génétique), Interleukine-6 (immunologie), Interleukine-8 (génétique), Interleukine-8 (immunologie), Lignée cellulaire, Macrophages (immunologie), Protéines de l'enveloppe virale (immunologie), Syndrome respiratoire aigu sévère (génétique), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (immunologie).
- MESH :
- génétique : Facteur de transcription RelA, Interleukine-6, Interleukine-8, Syndrome respiratoire aigu sévère.
- immunologie : Facteur de transcription RelA, Glycoprotéines membranaires, Interleukine-6, Interleukine-8, Macrophages, Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère, Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Cellules cultivées, Expression des gènes, Glycoprotéine de spicule des coronavirus, Humains, Lignée cellulaire.
English descriptors
- KwdEn :
- Cell Line, Cells, Cultured, Gene Expression, Humans, Interleukin-6 (genetics), Interleukin-6 (immunology), Interleukin-8 (genetics), Interleukin-8 (immunology), Macrophages (immunology), Membrane Glycoproteins (immunology), SARS Virus (immunology), Severe Acute Respiratory Syndrome (genetics), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (virology), Spike Glycoprotein, Coronavirus, Transcription Factor RelA (genetics), Transcription Factor RelA (immunology), Viral Envelope Proteins (immunology).
- MESH :
- chemical , genetics : Interleukin-6, Interleukin-8, Transcription Factor RelA.
- chemical , immunology : Interleukin-6, Interleukin-8, Membrane Glycoproteins, Transcription Factor RelA, Viral Envelope Proteins.
- genetics : Severe Acute Respiratory Syndrome.
- immunology : Macrophages, SARS Virus, Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Cell Line, Cells, Cultured, Gene Expression, Humans, Spike Glycoprotein, Coronavirus.
Abstract
A purified recombinant spike (S) protein was studied for its effect on stimulating human peripheral blood monocyte macrophages (PBMC). We examined inflammatory gene mRNA abundances found in S protein-treated PBMC using gene arrays. We identified differential mRNA abundances of genes with functional properties associated with antiviral (CXCL10) and inflammatory (IL-6 and IL-8) responses. We confirmed cytokine mRNA increases by real-time quantitative(q) RT-PCR or ELISA. We further analyzed the sensitivity and specificity of the prominent IL-8 response. By real-time qRT-PCR, S protein was shown to stimulate IL-8 mRNA accumulation in a dose dependent manner while treatment with E protein did not. Also, titration of S protein-specific production and secretion of IL-8 by ELISA showed that the dose of 5.6 nM of S produced a significant increase in IL-8 (
Url:
DOI: 10.1016/j.virusres.2009.01.005
PubMed: 19185596
PubMed Central: 2699111
Affiliations:
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Le document en format XML
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<term>Cells, Cultured</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Interleukin-6 (genetics)</term>
<term>Interleukin-6 (immunology)</term>
<term>Interleukin-8 (genetics)</term>
<term>Interleukin-8 (immunology)</term>
<term>Macrophages (immunology)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (genetics)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Transcription Factor RelA (genetics)</term>
<term>Transcription Factor RelA (immunology)</term>
<term>Viral Envelope Proteins (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Cellules cultivées</term>
<term>Expression des gènes</term>
<term>Facteur de transcription RelA (génétique)</term>
<term>Facteur de transcription RelA (immunologie)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Humains</term>
<term>Interleukine-6 (génétique)</term>
<term>Interleukine-6 (immunologie)</term>
<term>Interleukine-8 (génétique)</term>
<term>Interleukine-8 (immunologie)</term>
<term>Lignée cellulaire</term>
<term>Macrophages (immunologie)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (génétique)</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virus du SRAS (immunologie)</term>
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<term>Interleukin-8</term>
<term>Transcription Factor RelA</term>
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<term>Interleukin-8</term>
<term>Membrane Glycoproteins</term>
<term>Transcription Factor RelA</term>
<term>Viral Envelope Proteins</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term>
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<term>Interleukine-6</term>
<term>Interleukine-8</term>
<term>Syndrome respiratoire aigu sévère</term>
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<term>Glycoprotéines membranaires</term>
<term>Interleukine-6</term>
<term>Interleukine-8</term>
<term>Macrophages</term>
<term>Protéines de l'enveloppe virale</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
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<front><div type="abstract" xml:lang="en"><p>A purified recombinant spike (S) protein was studied for its effect on stimulating human peripheral blood monocyte macrophages (PBMC). We examined inflammatory gene mRNA abundances found in S protein-treated PBMC using gene arrays. We identified differential mRNA abundances of genes with functional properties associated with antiviral (CXCL10) and inflammatory (IL-6 and IL-8) responses. We confirmed cytokine mRNA increases by real-time quantitative(q) RT-PCR or ELISA. We further analyzed the sensitivity and specificity of the prominent IL-8 response. By real-time qRT-PCR, S protein was shown to stimulate IL-8 mRNA accumulation in a dose dependent manner while treatment with E protein did not. Also, titration of S protein-specific production and secretion of IL-8 by ELISA showed that the dose of 5.6 nM of S produced a significant increase in IL-8 (<italic>p</italic>
= 0.003) compared to mock-treated controls. The increase in IL-8 stimulated by a concentration of 5.6 nM of S was comparable to concentrations seen for S protein binding to ACE2 or to neutralizing monoclonal antibody suggesting a physiological relevance. An NF-κB inhibitor, TPCK (N-Tosyl-L-Phenylalanine Chloromethyl Ketone) could suppress IL-8 production and secretion in response to S protein in PBMC and THP-1 cells and in HCoV-229E virus-infected PBMC. Activation and translocation of NF-κB was shown to occur rapidly following exposure of PBMC or THP-1 cells to S protein using a highly sensitive assay for active nuclear NF-κB p65 transcription factor. The results further suggested that released or secreted S protein could activate blood monocytes through recognition by toll-like receptor (TLR)2 ligand.</p>
</div>
</front>
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</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>État de New York</li>
</region>
</list>
<tree><country name="États-Unis"><region name="État de New York"><name sortKey="Dosch, Susan F" sort="Dosch, Susan F" uniqKey="Dosch S" first="Susan F." last="Dosch">Susan F. Dosch</name>
</region>
<name sortKey="Collins, Arlene R" sort="Collins, Arlene R" uniqKey="Collins A" first="Arlene R." last="Collins">Arlene R. Collins</name>
<name sortKey="Mahajan, Supriya D" sort="Mahajan, Supriya D" uniqKey="Mahajan S" first="Supriya D." last="Mahajan">Supriya D. Mahajan</name>
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