ArticleHeliyon2021
SARS-CoV-2 spike protein S1 subunit induces pro-inflammatory responses via toll-like receptor 4 signaling in murine and human macrophages.
Article in Heliyon, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
178 citing papers in PubMed, 2 syntheses or guidelines pooled it, 266 citations in OpenAlex.
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Shared inflammatory pathways and therapeutic strategies in COVID-19 and cancer immunotherapy.Journal for immunotherapy of cancer · 2021Pooled it
- Intranasal drop of multiplex RNA therapy for SARS-CoV-2 infections: baicalein-enhanced FEN1 nuclease cleaving as a virus buster.Emerging microbes & infections · 2026Article
- Molecular, cellular and network mapping of brain structural deviations in patients with Post-COVID19 syndrome.Brain, behavior, & immunity - health · 2026Article
- In Silico Modeling of Structural Compatibility and Alignment Between Viral Class I Fusion Cores and Human TLR4/MD-2.International journal of molecular sciences · 2026Article
- Structural insights into TLR4 activation by SARS-CoV-2 spike protein: implications for inflammatory response modulation.Molecular diversity · 2026Article
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- FNDC4 and FNDC5 Attenuate SARS-CoV-2 S1-Induced Inflammatory Responses in Human Adipose Tissue.European journal of clinical investigation · 2026Article
- Radiofrequency Fields at 2.45 GHz Reprogram Mitochondria-Lysosome Crosstalk and Modulate the Survival/Death of Macrophages Exposed to LPS and/or the SARS-CoV-2 Spike Protein.International journal of molecular sciences · 2026Article
- Mesenchymal Stromal Cells Respond to SARS-CoV-2 Peptides and Exhibit Altered T-Cell Regulatory Capacity.Cells · 2026Article
- Divergent Inflammatory Profiles but No Predictive Biomarkers of Psychiatric Sequelae After Viral Infection: A 12-Month Cohort Study.International journal of molecular sciences · 2026Article
- Mechanistic insights into the impact of prenatal viral infections on maternal and offspring immunity.Npj viruses · 2026Review
- Recombinant SARS-Cov-2 spike protein S1 subunit upregulates P2 × 7-NLRP3 leading to macrophage pyroptosis promoting acute lung injury.Respiratory research · 2026Article
- Targeting PTP4A3 with KVX-053 mitigates alcohol-amplified SARS-CoV-2 spike protein-induced acute lung injury.Frontiers in pharmacology · 2026Article
- Benzydamine Attenuates Matrix Metalloproteinase-9 Expression Through Inhibition of ERK MAPK in Activated Human Monocytic Cells Under Hyperglycemic Condition.Mediators of inflammation · 2026Article
- Early monocyte subset signatures predict outcomes in unvaccinated COVID-19 patients.Frontiers in immunology · 2026Article
- A SARS-CoV-2 spike-derived adjuvant peptide boosts IL-17/IFN-γ immunity and improves anti-PD-L1 therapy against melanoma.Molecular medicine (Cambridge, Mass.) · 2025Article
- SARS-CoV-2 innate immune recognition and implications for respiratory health.Cytokine & growth factor reviews · 2025Review
- Per- and Polyfluoroalkyl Substances (PFAS) Enhance Cholesterol Accumulation and Dysregulate Inflammatory Responses in Macrophages.Cardiovascular toxicology · 2025Article
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
118 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now spread globally. Some patients develop severe complications including multiple organ failure. It has been suggested that excessive inflammation associated with the disease plays major role in the severity and mortality of COVID-19. To elucidate the inflammatory mechanisms involved in COVID-19, we examined the effects of SARS-CoV-2 spike protein S1 subunit (hereafter S1) on the pro-inflammatory responses in murine and human macrophages. Murine peritoneal exudate macrophages produced pro-inflammatory mediators in response to S1 exposure. Exposure to S1 also activated nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) signaling pathways. Pro-inflammatory cytokine induction by S1 was suppressed by selective inhibitors of NF-κB and JNK pathways. Treatment of murine peritoneal exudate macrophages and human THP-1 cell-derived macrophages with a toll-like receptor 4 (TLR4) antagonist attenuated pro-inflammatory cytokine induction and the activation of intracellular signaling by S1 and lipopolysaccharide. Similar results were obtained in experiments using TLR4 siRNA-transfected murine RAW264.7 macrophages. In contrast, TLR2 neutralizing antibodies could not abrogate the S1-induced pro-inflammatory cytokine induction in either RAW264.7 or THP-1 cell-derived macrophages. These results suggest that SARS-CoV-2 spike protein S1 subunit activates TLR4 signaling to induce pro-inflammatory responses in murine and human macrophages. Therefore, TLR4 signaling in macrophages may be a potential target for regulating excessive inflammation in COVID-19 patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.