ArticleMediators of inflammation2016
Bidirectional Crosstalk between C5a Receptors and the NLRP3 Inflammasome in Macrophages and Monocytes.
Article in Mediators of inflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- Mitochondria: The Crossroads of Complement Activation and Kidney Injury Progression.International journal of molecular sciences · 2026Review
- Complement and inflammasome crosstalk in chronic inflammation.Frontiers in immunology · 2026Review
- Targeting innate immunity to modulate bone metabolism: a novel strategy for osteoporosis treatment.Frontiers in aging · 2026Review
- Molecular Evolution of the NLR Gene Family Reveals Diverse Innate Immune Strategies in Bats.Biomolecules · 2025Article
- Post-ischemia and reperfusion kidney injury is mitigated in a novel complement 5 knockout rat.Physiological reports · 2025Article
- Cholesterol crystal embolization induced kidney disease.American heart journal plus : cardiology research and practice · 2025Article
- Schwann cell C5aR1 co-opts inflammasome NLRP1 to sustain pain in a mouse model of endometriosis.Nature communications · 2024Article
- Cell-intrinsic C5a synergizes with Dectin-1 in macrophages to mediate fungal killing.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- FBXO11 governs macrophage cell death and inflammation in response to bacterial toxins.Life science alliance · 2023Article
- Comparative analyses of bat genomes identify distinct evolution of immunity in Old World fruit bats.Science advances · 2023Article
- The role of the complosome in health and disease.Frontiers in immunology · 2023Review
- The Complement Pathway: New Insights into Immunometabolic Signaling in Diabetic Kidney Disease.Antioxidants & redox signaling · 2022Review
- Microglia as Therapeutic Target for Radiation-Induced Brain Injury.International journal of molecular sciences · 2022Review
- Hematopoiesis and innate immunity: an inseparable couple for good and bad times, bound together by an hormetic relationship.Leukemia · 2022Review
- Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation.Science immunology · 2021Article
- Antibody and Protein Profiles in Glaucoma: Screening of Biomarkers and Identification of Signaling Pathways.Biology · 2021Review
- The roles and potential therapeutic implications of C5a in the pathogenesis of COVID-19-associated coagulopathy.Cytokine & growth factor reviews · 2021Review
- Article
- More than a Pore: Nonlytic Antimicrobial Functions of Complement and Bacterial Strategies for Evasion.Microbiology and molecular biology reviews : MMBR · 2021Review
- Renal diseases and the role of complement: Linking complement to immune effector pathways and therapeutics.Advances in immunology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
C5a is an inflammatory mediator generated by complement activation that positively regulates various arms of immune defense, including Toll-like receptor 4 (TLR4) signaling. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is activated by pathogen products and cellular/tissue damage products and is a major contributor of IL-1β. In this study, we investigate whether C5a modulates lipopolysaccharide- (LPS-) induced NLRP3 inflammasome activation in myeloid cells. Appearance of plasma IL-1β during endotoxemia was reduced in C5aR1(-/-) mice when compared to wild-type mice. In vitro, C5a significantly enhanced LPS-induced production of IL-1β in bone marrow Ly6C-high inflammatory monocytes, accompanied by augmented intracellular pro-IL-1β expression. This effect was abolished during p38 blockade by SB 203580 and in the absence of C5aR1. Conversely, C5a suppressed LPS-induced macrophage production of IL-1β, which was accompanied by attenuated levels of pro-IL-1β, NLRP3, and caspase-1 expression. C5a's suppressive effects were negated during phosphoinositide 3-kinase (PI3K) inhibition by wortmannin but were largely preserved in the absence of C5aR1. Thus, C5a bidirectionally amplifies TLR4-mediated NLRP3 inflammasome activation in monocytes while suppressing this pathway in macrophages. However, as C5aR1 deficiency attenuates the IL-1β response to LPS challenge in vivo, our results suggest overall that C5a augments physiologic inflammasome responses.
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Registered trials
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.