Evidence map›Paper›PMID 20506351›Full record

ArticleArthritis and rheumatism2010

Role of the leucine-rich repeat domain of cryopyrin/NALP3 in monosodium urate crystal-induced inflammation in mice.

Hal M Hoffman, Peter Scott, James L Mueller, Amir Misaghi, Sean Stevens, George D Yancopoulos, Andrew Murphy, David M Valenzuela, Ru Liu-Bryan

Abstract read
In one paragraph

Article in Arthritis and rheumatism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
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  13. Review
  14. Evidence-based complementary and alternative medicine : eCAM · 2020
    Article
  15. Article
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  17. Review
  18. Article
  19. Article
  20. COPs and POPs Patrol Inflammasome Activation.Journal of molecular biology · 2018
    Review
4 · The record

Corrections and comments

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

9 authors at 3 institutions in 1 country.

Hal M HoffmanUniversity of California, San Diego, USA.
Peter Scott
James L Mueller
Amir Misaghi
Sean Stevens
George D Yancopoulos
Andrew Murphy
David M Valenzuela
Ru Liu-Bryan
Regeneron (United States) · USUniversity of California, San Diego · USUniversity of California San Diego Medical Center · US

Funding

The Role of Cryopyrin in Autoinflammatory DiseasesR01AI052430 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HOFFMAN, HAROLD M · 2002 to 2011
$3.4M
Innate Immunity in gouty InflammationR21AI067966 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI BRYAN, RU · 2007 to 2008
$377k
NIAID NIH HHS AI-52430NIAID NIH HHS R01 AI052430NIAID NIH HHS R21 AI067966NIAMS NIH HHS AR-1067966
6 · The paper itself

Abstract

objectiveThe mechanism by which monosodium urate monohydrate (MSU) crystals intracellularly activate the cryopyrin inflammasome is unknown. The aim of this study was to use a mouse molecular genetics-based approach to test whether the leucine-rich repeat (LRR) domain of cryopyrin is required for MSU crystal-induced inflammation.

methodsCryopyrin-knockout lacZ (Cryo(-Z/-Z)) mice and mice with the cryopyrin LRR domain deleted and fused to the lacZ reporter (Cryo(DeltaLRR Z/DeltaLRR Z)) were generated using bacterial artificial chromosome-based targeting vectors, which allow for large genomic deletions. Bone marrow-derived macrophages from Cryo(DeltaLRR Z/DeltaLRR Z) mice, Cryo(-Z/-Z) mice, and congenic wild-type (WT) mice were challenged with endotoxin-free MSU crystals under serum-free conditions. Phagocytosis and cytokine expression were assessed by flow cytometry and enzyme-linked immunosorbent assay. MSU crystals also were injected into mouse synovial-like subcutaneous air pouches. The in vivo inflammatory responses were examined.

resultsRelease of interleukin-1beta (IL-1beta), but not CXCL1 and tumor necrosis factor alpha, was impaired in Cryo(DeltaLRR Z/DeltaLRR Z) and Cryo(-Z/-Z) mouse bone marrow-derived macrophages compared with WT mouse bone marrow-derived macrophages in response to not only MSU crystals but also other known stimuli that activate the cryopyrin inflammasome. In addition, a comparable percentage of MSU crystals taken up by each type of bone marrow-derived macrophage was observed. Moreover, total leukocyte infiltration in the air pouch and IL-1beta production were attenuated in Cryo(-Z/-Z) and Cryo(DeltaLRR Z/DeltaLRR Z) mice at 6 hours postinjection of MSU crystals compared with WT mice.

conclusionMSU crystal-induced inflammatory responses were comparably attenuated both in vitro and in vivo in Cryo(DeltaLRR Z/DeltaLRR Z) and Cryo(-Z/-Z) mice. Hence, the LRR domain of cryopyrin plays a role in mediating MSU crystal-induced inflammation in this model.

Indexed as

Repetitive Sequences, Amino AcidAnimalsArthritis, GoutyBone Marrow CellsCarrier ProteinsCells, CulturedCytokinesFemaleLeucine-Rich Repeat ProteinsMacrophage ActivationMacrophagesMaleMiceMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinPhagocytosisCarrier ProteinsCytokinesLeucine-Rich Repeat ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseProteinsUric Acid

Identifiers

PMID20506351
PMCPMC2929807
OpenAlexW1845148795

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.