ArticleCell death & disease2019
Inhibition of transmembrane TNF-α shedding by a specific antibody protects against septic shock.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- Adipocyte-Derived Leptolin Enhances Energy Expenditure and Prevents Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immunization with detoxified TNFα elicits neutralizing antibodies and ameliorates inflammatory shock and autoimmune arthritis in mice.Frontiers in immunology · 2026Article
- Endurance training increases tmTNF-α and IL-6 levels in several vital organs in rats: relationship with hypoxia markers.Frontiers in molecular biosciences · 2026Article
- Predicting Clinical Response to Granulocyte/Monocyte Adsorption Apheresis in Treatment-Resistant Ulcerative Colitis.Gastro hep advances · 2026Article
- ADAM17 as a proteolytic rheostat linking inflammation, tissue repair, and failure of inflammatory resolution in liver injury and fibrosis.Frontiers in pharmacology · 2026Review
- Myeloid ADAM17 induces ST2Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Role of Necroptosis, a Regulated Cell Death, in Seizure and Epilepsy.Neurochemical research · 2024Review
- Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.Burns & trauma · 2024Review
- Article
- Preeclampsia promotes autism in offspring via maternal inflammation and fetal NFκB signaling.Life science alliance · 2023Article
- Short Peptides of Innate Immunity Protein Tag7 (PGLYRP1) Selectively Induce Inhibition or Activation of Tumor Cell Death via TNF Receptor.International journal of molecular sciences · 2023Article
- Triad3A involved in the regulation of endotoxin tolerance and mycobactericidal activity through the NFκB-nitric oxide pathway.Immunity, inflammation and disease · 2023Article
- Antitumor effect of CAR-T cells targeting transmembrane tumor necrosis factor alpha combined with PD-1 mAb on breast cancers.Journal for immunotherapy of cancer · 2023Article
- Clinical Outcome Prediction in COVID-19 Patients by Lymphocyte Subsets Analysis and Monocytes' iTNF-α Expression.Biology · 2021Article
- Suppression of Transmembrane Tumor Necrosis Factor Alpha Processing by a Specific Antibody Protects Against Colitis-Associated Cancer.Frontiers in immunology · 2021Article
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- Blocking ADAM17 Function with a Monoclonal Antibody Improves Sepsis Survival in a Murine Model of Polymicrobial Sepsis.International journal of molecular sciences · 2020Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transmembrane TNF-α (tmTNF-α) and secretory TNF-α (sTNF-α) display opposite effects in septic shock. Reducing tmTNF-α shedding can offset the detrimental effects of sTNF-α and increase the beneficial effect of tmTNF-α. We previously developed a monoclonal antibody that is specific for tmTNF-α and does not cross-react with sTNF-α. In this study, we show that this antibody can specifically suppress tmTNF-α shedding by competing with a TNF-α converting enzyme that cleaves the tmTNF-α ectodomain to release sTNF-α. This tmTNF-α antibody significantly inhibited LPS-induced secretion of interleukin (IL)-1β, IL-6, interferon-β, and nitric oxide by monocytes/macrophages, and protected mice from septic shock induced by lipopolysaccharide (LPS) or cecal ligation and puncture, while reducing the bacterial load. The mechanism associated with the protective effect of this tmTNF-α antibody involved promotion of LPS-induced toll-like receptor 4 (TLR4) internalization and degradation by recruiting Triad3A to TLR4. Moreover, the tmTNF-α antibody inhibited LPS-induced activation of nuclear factor-κB and interferon regulatory factor 3 pathways by upregulating expression of A20 and monocyte chemotactic protein-induced protein 1. Similarly, treatment of macrophages with exogenous tmTNF-α suppressed LPS/TLR4 signaling and release of proinflammatory cytokines, indicating that increased levels of tmTNF-α promoted by the antibody contributed to its inhibitory effect. Thus, use of this tmTNF-α antibody for specific suppression of tmTNF-α shedding may be a promising strategy to treat septic shock.
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