ArticlePloS one2011
Pre-treatment of recombinant mouse MFG-E8 downregulates LPS-induced TNF-α production in macrophages via STAT3-mediated SOCS3 activation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 84 citations in OpenAlex.
- Targeting Frequent Efferocytosis in Tumor Microenvironment is a New Direction for Cancer Treatment.Small science · 2025Review
- MFG-E8 in Kawasaki Disease: Role in Endothelial Injury and Diagnostic Potential.Journal of inflammation research · 2025Article
- Potent CTLs can be induced against tumor cells in an environment of lower levels of systemic MFG-E8.Cancer science · 2024Article
- The Regulatory Roles ofInternational journal of molecular sciences · 2023Article
- Milk fat-globule epidermal growth factor 8: A potential Regulator of Cutaneous Wound Healing.Molecular biology reports · 2022Review
- MFG-E8 Reduces Aortic Intimal Proliferation in a Murine Model of Transplant Vasculopathy.International journal of molecular sciences · 2022Article
- The preparation technology and application of xylo-oligosaccharide as prebiotics in different fields: A review.Frontiers in nutrition · 2022Review
- MFG-E8 Knockout Aggravated Nonalcoholic Steatohepatitis by Promoting the Activation of TLR4/NF-Mediators of inflammation · 2022Article
- Extracellular CIRP activates STING to exacerbate hemorrhagic shock.JCI insight · 2021Article
- MFG-E8 Plays an Important Role in Attenuating Cerulein-Induced Acute Pancreatitis in Mice.Cells · 2021Article
- Milk fat globule EGF factor 8 restores mitochondrial function via integrin-medicated activation of the FAK-STAT3 signaling pathway in acute pancreatitis.Clinical and translational medicine · 2021Article
- SOCS Proteins in Immunity, Inflammatory Diseases, and Immune-Related Cancer.Frontiers in medicine · 2021Review
- Article
- Nrf2-SHP Cascade-Mediated STAT3 Inactivation Contributes to AMPK-Driven Protection Against Endotoxic Inflammation.Frontiers in immunology · 2020Article
- MFG-E8 mediates arterial aging by promoting the proinflammatory phenotype of vascular smooth muscle cells.Journal of biomedical science · 2019Article
- Physostigmine Restores Impaired Autophagy in the Rat Hippocampus after Surgery Stress and LPS Treatment.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2018Article
- Multifaceted Roles for Macrophages in Prostate Cancer Skeletal Metastasis.Frontiers in endocrinology · 2018Review
- Genomic and lipidomic analyses differentiate the compensatory roles of two COX isoforms during systemic inflammation in mice.Journal of lipid research · 2018Article
- Deficiency in milk fat globule-epidermal growth factor-factor 8 exacerbates organ injury and mortality in neonatal sepsis.Journal of pediatric surgery · 2017Article
- Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Milk fat globule-epidermal growth factor factor 8 (MFG-E8) regulates innate immune function by modulating cellular signaling, which is less understood. Herein, we aimed to investigate the direct anti-inflammatory role of MFG-E8 in macrophages by pre-treatment with recombinant murine MFG-E8 (rmMFG-E8) followed by stimulation with LPS in RAW264.7 cells and in peritoneal macrophages, isolated from wild-type (WT) or MFG-E8(-/-) mice. RAW264.7 cells and mouse peritoneal macrophages treated with rmMFG-E8 significantly downregulated LPS-induced TNF-α mRNA by 25% and 24%, and protein levels by 29% and 23%, respectively (P<0.05). Conversely, peritoneal macrophages isolated from MFG-E8(-/-) mice produced 28% higher levels of TNF-α, as compared to WT mice when treated with LPS. In in vivo, endotoxemia induced by intraperitoneal injection of LPS (5 mg/kg BW), at 4 h after induction, serum level of TNF-α was significantly higher in MFG-E8(-/-) mice (837 pg/mL) than that of WT (570 pg/mL, P<0.05). To elucidate the direct anti-inflammatory effect of MFG-E8, we examined STAT3 and its target gene, SOCS3. Treatment with rmMGF-E8 significantly induced pSTAT3 and SOCS3 in macrophages. Similar results were observed in in vivo treatment of rmMFG-E8 in peritoneal cells and splenic tissues. Pre-treatment with rmMFG-E8 significantly reduced LPS-induced NF-κB p65 contents. These data clearly indicated that rmMFG-E8 upregulated SOCS3 which in turn interacted with NF-κB p65, facilitating negative regulation of TLR4 signaling for LPS-induced TNF-α production. Our findings strongly suggest that MFG-E8 is a direct anti-inflammatory molecule, and that it could be developed as a therapy in attenuating inflammation and tissue injury.
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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.