ArticleScientific reports2015
A Novel Role of Numb as A Regulator of Pro-inflammatory Cytokine Production in Macrophages in Response to Toll-like Receptor 4.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
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- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
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- NUMB attenuates posttraumatic osteoarthritis by inhibiting BTRC and inactivating the NF-κB pathway.Journal of orthopaedic surgery and research · 2024Article
- Lipocalin 2 activates the NLRP3 inflammasome via LPS‑induced NF‑κB signaling and plays a role as a pro‑inflammatory regulator in murine macrophages.Molecular medicine reports · 2022Article
- miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB.Cartilage · 2021Article
- Anti-Inflammatory Effects of the Fraction from the Leaves ofEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Resolvin D5, a Lipid Mediator, Inhibits Production of Interleukin-6 and CCL5 Via the ERK-NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated THP-1 Cells.Journal of microbiology and biotechnology · 2020Article
- microRNA-146a-5p association with the cardiometabolic disease risk factor TMAO.Physiological genomics · 2019Article
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- Toll-Like Receptor 4 (TLR4) Expression Affects Schwann Cell Behavior in vitro.Scientific reports · 2018Article
- Tenascin-c renders a proangiogenic phenotype in macrophage via annexin II.Journal of cellular and molecular medicine · 2018Article
- CP and CP-PGN protect mice against MRSA infection by inducing M1 macrophages.Scientific reports · 2017Article
- Nanocarrier-mediated delivery of α-mangostin for non-surgical castration of male animals.Scientific reports · 2017Article
- Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case-control study.BMJ paediatrics open · 2017Article
- Inflammation and Notch signaling: a crosstalk with opposite effects on tumorigenesis.Cell death & disease · 2016Review
- Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways.Scientific reports · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of macrophages triggers the release of pro-inflammatory cytokines leading to inflammation. Numb is a negative regulator of Notch signaling, but the role of Numb in macrophages is not fully understood. In this study, the role of Numb as a regulator of inflammatory responses in macrophages was investigated. Murine bone marrow-derived macrophages, in which expression of Numb was silenced, secreted significantly less TNFα, IL-6 and IL-12 and more IL-10 upon activation by lipopolysaccharide (LPS), a ligand for Toll-like receptor 4 (TLR4), despite increased Notch signaling. The Tnfα mRNA levels both in Numb-deficient and wild-type macrophages were not significantly different, unlike those of Il6 and Il12-p40. In Numb-deficient macrophages, the Tnfα mRNAs were degraded at faster rate, compared to those in control macrophages. Activation of p38 MAPK and NF-κΒ p65 were compromised in activated Numb deficient macrophages. Numb was found to interact with the E3 ubiquitin ligase, Itch, which reportedly regulates p38 MAPK. In addition, blocking the Notch signaling pathway in activated, Numb-deficient macrophages did not further reduce TNFα levels, suggesting a Notch-independent role for Numb. A proteomics approach revealed a novel function for Numb in regulating complex signaling cascades downstream of TLRs, partially involving Akt/NF-κB p65/p38 MAPK in macrophages.
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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.