ArticleProceedings of the National Academy of Sciences of the United States of America2021
Galectin-3 promotes noncanonical inflammasome activation through intracellular binding to lipopolysaccharide glycans.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Early postoperative galectin-3 for risk stratification of delayed graft function after kidney transplantation.Clinical kidney journal · 2026Article
- Expression, Localization and Actions of Galectin-3: Implications in the Pathophysiology and Therapy of Cardiovascular Disease.International journal of molecular sciences · 2026Review
- Decoding the Gut-Fat-Heart Axis: From Molecular Communication Networks to Clinical Translation Strategies.International journal of molecular sciences · 2026Review
- Galectin-3 Mediates Heme-Induced Multi-Organ Dysfunction by Modulating the Splenic Immune Microenvironment.Diseases (Basel, Switzerland) · 2026Article
- SOX9 represses the human galectin-3 promoter in SW1353 cells: potential implications for osteoarthritis.Scientific reports · 2026Article
- When glycobiology meets inflammasome activation: Insights and implications.Journal of advanced research · 2026Review
- The Historiography of Galactose and Its Recognition by Galectins.Advances in experimental medicine and biology · 2026Review
- A Narrative Review on the Multifaceted Roles of Galectins in Host-Pathogen Interactions DuringInternational journal of molecular sciences · 2025Review
- Review
- Protective immune response against Rhodococcus equi: An innate immunity-focused review.Equine veterinary journal · 2025Review
- Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication.Molecular cancer · 2024Review
- The immune interactions of gut glycans and microbiota in health and disease.Molecular microbiology · 2024Review
- The Possible Effects of Galectin-3 on Mechanisms of Renal and Hepatocellular Injury Induced by Intravascular Hemolysis.International journal of molecular sciences · 2024Review
- The role of galectins in the regulation of autophagy and inflammasome in host immunity.Seminars in immunopathology · 2024Review
- Galectin-3 is upregulated in frontotemporal dementia patients with subtype specificity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Biophysical and Structural Characterization of the Interaction between Human Galectin-3 and the Lipopolysaccharide fromInternational journal of molecular sciences · 2024Article
- The role of galectins in immunity and infection.Nature reviews. Immunology · 2023Review
- Elevated Galectin-3 Is Associated with Aging, Multiple Sclerosis, and Oxidized Phosphatidylcholine-Induced Neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Cytosolic galectin-4 enchains bacteria, restricts their motility, and promotes inflammasome activation in intestinal epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A single dose of lipopolysaccharide elicits autofluorescence in the mouse brain.Frontiers in aging neuroscience · 2023Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytosolic lipopolysaccharides (LPSs) bind directly to caspase-4/5/11 through their lipid A moiety, inducing inflammatory caspase oligomerization and activation, which is identified as the noncanonical inflammasome pathway. Galectins, β-galactoside-binding proteins, bind to various gram-negative bacterial LPS, which display β-galactoside-containing polysaccharide chains. Galectins are mainly present intracellularly, but their interactions with cytosolic microbial glycans have not been investigated. We report that in cell-free systems, galectin-3 augments the LPS-induced assembly of caspase-4/11 oligomers, leading to increased caspase-4/11 activation. Its carboxyl-terminal carbohydrate-recognition domain is essential for this effect, and its N-terminal domain, which contributes to the self-association property of the protein, is also critical, suggesting that this promoting effect is dependent on the functional multivalency of galectin-3. Moreover, galectin-3 enhances intracellular LPS-induced caspase-4/11 oligomerization and activation, as well as gasdermin D cleavage in human embryonic kidney (HEK) 293T cells, and it additionally promotes interleukin-1β production and pyroptotic death in macrophages. Galectin-3 also promotes caspase-11 activation and gasdermin D cleavage in macrophages treated with outer membrane vesicles, which are known to be taken up by cells and release LPSs into the cytosol. Coimmunoprecipitation confirmed that galectin-3 associates with caspase-11 after intracellular delivery of LPSs. Immunofluorescence staining revealed colocalization of LPSs, galectin-3, and caspase-11 independent of host
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