ArticleProceedings of the National Academy of Sciences of the United States of America2019
HMGB1-C1q complexes regulate macrophage function by switching between leukotriene and specialized proresolving mediator biosynthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 84 citations in OpenAlex.
- Complement Activation by Post-Translationally Modified Proteins: Links to Chronic Inflammation and Autoimmunity.Immunological reviews · 2026Review
- Regulatory effects and mechanisms of the acupuncture-induced complement component 1q on the high mobility group box 1 -receptor for advanced glycation end products-nuclear factor kappa-B pathway at Zusanli (ST36).Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Vagus nerve control of HMGB1 accessibility: a bioelectronic strategy for inflammation and pain.Bioelectronic medicine · 2026Review
- Targeting Complement Component 1q Ameliorates Diabetic Endothelial Inflammation Via Orphan Nuclear Receptor 4a1-Dependent Suppression of Nuclear Factor κB Signaling.Journal of the American Heart Association · 2026Article
- Elucidation of a potent pro-resolving mediator of inflammation resolution via human neutrophil-vascular endothelial cell interactions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hormone-sensitive lipase drives pro-resolving macrophage polarization and enhances efferocytosis.Cell communication and signaling : CCS · 2026Article
- Pharmacological intervention of the HMGB1-pCTS-L axis to ameliorate inflammatory diseases.Frontiers in immunology · 2026Review
- Inhibitory pattern recognition receptors: lessons from LAIR1.Nature reviews. Immunology · 2025Review
- Knowing the enemy: strategic targeting of complement to treat Alzheimer disease.Nature reviews. Neurology · 2025Review
- Role of the Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Inflammatory Responses.Biomolecules · 2024Review
- Low-dose pro-resolving mediators temporally reset the resolution response to microbial inflammation.Molecular medicine (Cambridge, Mass.) · 2024Article
- YAP activation in liver macrophages via depletion of MST1/MST2 enhances liver inflammation and fibrosis in MASLD.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Wilson's Disease-Crossroads of Genetics, Inflammation and Immunity/Autoimmunity: Clinical and Molecular Issues.International journal of molecular sciences · 2024Review
- Impact of microglia isolation and culture methodology on transcriptional profile and function.Journal of neuroinflammation · 2024Article
- Lupus autoantibodies initiate neuroinflammation sustained by continuous HMGB1:RAGE signaling and reversed by increased LAIR-1 expression.Nature immunology · 2024Article
- Macrophage RAGE activation is proinflammatory in NASH.JCI insight · 2024Article
- Complement C1q is a key player in tumor-associated macrophage-mediated CD8International journal of biological sciences · 2024Article
- Potential regulatory role of the Nrf2/HMGB1/TLR4/NF-κB signaling pathway in lupus nephritis.Pediatric rheumatology online journal · 2023Article
- Glucocorticoids regulate lipid mediator networks by reciprocal modulation of 15-lipoxygenase isoforms affecting inflammation resolution.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Resolvin D1 prevents injurious neutrophil swarming in transplanted lungs.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
5 more citing papers are in PubMed but not listed here.
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9 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophage polarization is critical to inflammation and resolution of inflammation. We previously showed that high-mobility group box 1 (HMGB1) can engage receptor for advanced glycation end product (RAGE) to direct monocytes to a proinflammatory phenotype characterized by production of type 1 IFN and proinflammatory cytokines. In contrast, HMGB1 plus C1q form a tetramolecular complex cross-linking RAGE and LAIR-1 and directing monocytes to an antiinflammatory phenotype. Lipid mediators, as well as cytokines, help establish a milieu favoring either inflammation or resolution of inflammation. This study focuses on the induction of lipid mediators by HMGB1 and HMGB1 plus C1q and their regulation of IRF5, a transcription factor critical for the induction and maintenance of proinflammatory macrophages. Here, we show that HMGB1 induces leukotriene production through a RAGE-dependent pathway, while HMGB1 plus C1q induces specialized proresolving lipid mediators lipoxin A4, resolvin D1, and resolvin D2 through a RAGE- and LAIR-1-dependent pathway. Leukotriene exposure contributes to induction of IRF5 in a positive-feedback loop. In contrast, resolvins (at 20 nM) block IRF5 induction and prevent the differentiation of inflammatory macrophages. Finally, we have generated a molecular mimic of HMGB1 plus C1q, which cross-links RAGE and LAIR-1 and polarizes monocytes to an antiinflammatory phenotype. These findings may provide a mechanism to control nonresolving inflammation in many pathologic conditions.
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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.