ArticleProceedings of the National Academy of Sciences of the United States of America2020
TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 99 citations in OpenAlex.
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- Distinct colitis-associated macrophages drive NOD2-dependent bacterial sensing and gut homeostasis.The Journal of clinical investigation · 2025Article
- Macrophage dynamics and the role of TREM2 at the oral mucosal barrier.Journal of translational medicine · 2025Article
- Toxicological Response of the BEAS-2B Cell After Acute Exposure at the Air-Liquid Interface to Ethylbenzene and m-Xylene Alone and in Binary Mixtures.Journal of applied toxicology : JAT · 2025Article
- Genome sequencing reveals CCDC88A variants in malformations of cortical development and immune dysfunction.Human molecular genetics · 2025Article
- Therapeutic effects of chlorogenic acid on allergic rhinitis through TLR4/MAPK/NF-κB pathway modulation.Biomolecules & biomedicine · 2025Article
- An in situ engineered chimeric IL-2 receptor potentiates the tumoricidal activity of proinflammatory CAR macrophages in renal cell carcinoma.Nature cancer · 2025Article
- GIV/Girdin Modulation of Microglial Activation in Ischemic Stroke: Impact of FTO-Mediated m6A Modification.Molecular neurobiology · 2025Article
- Lipopolysaccharide (LPS) induces sclerostin secretion by extracellular vesicle via TLR4/miR-92a-3p/PTEN/NF-κB signalling pathway in murine macrophage.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
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- The effect of Jian Gan powder on the proliferation, migration and polarization of macrophages and relative mechanism.Pharmaceutical biology · 2024Article
- GSP1-111 Modulates the Microglial M1/M2 Phenotype by Inhibition of Toll-like Receptor 2: A Potential Therapeutic Strategy for Depression.International journal of molecular sciences · 2024Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Sensing of pathogens by Toll-like receptor 4 (TLR4) induces an inflammatory response; controlled responses confer immunity but uncontrolled responses cause harm. Here we define how a multimodular scaffold, GIV (a.k.a. Girdin), titrates such inflammatory response in macrophages. Upon challenge with either live microbes or microbe-derived lipopolysaccharides (a ligand for TLR4), macrophages with GIV mount a more tolerant (hypo-reactive) transcriptional response and suppress proinflammatory cytokines and signaling pathways (i.e., NFkB and CREB) downstream of TLR4 compared to their GIV-depleted counterparts. Myeloid-specific gene-depletion studies confirmed that the presence of GIV ameliorates dextran sodium sulfate-induced colitis and sepsis-induced death. The antiinflammatory actions of GIV are mediated via its C-terminally located TIR-like BB-loop (TILL) motif which binds the cytoplasmic TIR modules of TLR4 in a manner that precludes receptor dimerization; such dimerization is a prerequisite for proinflammatory signaling. Binding of GIV's TILL motif to TIR modules inhibits proinflammatory signaling via other TLRs, suggesting a convergent paradigm for fine-tuning macrophage inflammatory responses.
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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.