Evidence map›Paper›PMID 38863059›Full record

ArticleArthritis research & therapy2024

The integrin CD11b inhibits MSU-induced NLRP3 inflammasome activation in macrophages and protects mice against MSU-induced joint inflammation.

Driss Ehirchiou, Ilaria Bernabei, Vishnuprabu Durairaj Pandian, Sonia Nasi, Veronique Chobaz, Mariela Castelblanco, Alexander So, Fabio Martinon, Xiaoyun Li, Hans Acha-Orbea and 3 more

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Article in Arthritis research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Driss EhirchiouService of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Ilaria BernabeiService of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Vishnuprabu Durairaj PandianDepartment of Physiology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, United States.
Sonia NasiService of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Veronique ChobazService of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Mariela CastelblancoService of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Alexander SoService of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Fabio MartinonDepartment of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Xiaoyun LiDepartment of Fundamental Oncology, University of Lausanne, Lausanne, Switzerland.
Hans Acha-OrbeaDepartment of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Thomas HugleService of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Li Zhang *Department of Physiology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, United States.
Nathalie Busso *Service of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. Nathalie.Busso@chuv.ch.

Funding

Fonds National Suisse de la recherche scientifique, Switzerland 310030_173134
6 · The paper itself

Abstract

objectiveIn gout, monosodium urate crystals are taken up by macrophages, triggering the activation of the NLRP3 inflammasome and the maturation of IL-1β. This study aimed to investigate the role of integrin CD11b in inflammasome activation in macrophages stimulated by MSU.

methodsBMDM from WT and CD11b KO mice were stimulated in vitro with MSU crystals. Cellular supernatants were collected to assess the expression of the inflammatory cytokines by enzyme-linked immunosorbent assay and western blot methods. The role of integrin CD11b in MSU-induced gouty arthritis in vivo was investigated by intra-articular injection of MSU crystals. Real-time extracellular acidification rate and oxygen consumption rate of BMDMs were measured by Seahorse Extracellular Flux Analyzer.

resultsWe demonstrate that CD11b-deficient mice developed exacerbated gouty arthritis with increased recruitment of leukocytes in the joint and higher IL-1β levels in the sera. In macrophages, genetic deletion of CD11b induced a shift of macrophage metabolism from oxidative phosphorylation to glycolysis, thus decreasing the overall generation of intracellular ATP. Upon MSU stimulation, CD11b-deficient macrophages showed an exacerbated secretion of IL-1β. Treating wild-type macrophages with a CD11b agonist, LA1, inhibited MSU-induced release of IL-1β in vitro and attenuated the severity of experimental gouty arthritis. Importantly, LA1, was also effective in human cells as it inhibited MSU-induced release of IL-1β by peripheral blood mononuclear cells from healthy donors.

conclusionOur data identified the CD11b integrin as a principal cell membrane receptor that modulates NLRP3 inflammasome activation by MSU crystal in macrophages, which could be a potential therapeutic target to treat gouty arthritis in human patients.

Indexed as

Arthritis, GoutyCD11b AntigenInflammasomesMacrophagesMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinUric AcidAnimalsMaleMiceCD11b AntigenInflammasomesItgam protein, mouseNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseUric AcidAnimal modelCD11bCD11b agonistIntegrinMSU crystalsNLRP3 inflammasome

Identifiers

PMID38863059
PMCPMC11165854

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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.