Evidence map›Paper›PMID 19950258›Full record

ArticleArthritis and rheumatism2009

Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation.

Monica Guma, Lisa Ronacher, Ru Liu-Bryan, Shinji Takai, Michael Karin, Maripat Corr

Open access · greenAbstract read
In one paragraph

Article in Arthritis and rheumatism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
156citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% 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

156 citing papers in PubMed, 1 synthesis or guideline pooled it, 304 citations in OpenAlex.

  1. Pooled it
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  15. Therapeutic effect ofFrontiers in pharmacology · 2024
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96 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Monica GumaUniversity of California at San Diego, La Jolla.
Lisa Ronacher
Ru Liu-Bryan
Shinji Takai
Michael Karin
Maripat Corr
University of California, San Diego · USOsaka Medical and Pharmaceutical University · JP

Funding

REGULATION OF NFKB AND IKK BY PROINFLAMMATORY STIMULIR01AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 1998 to 2017
$7.4M
NF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of InflammationR37AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin · 2018 to 2026
$6.0M
Stress Signaling Pathways in Toxicity and DiseaseR01ES006376 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 1993 to 2011
$4.3M
Cartilage Innate Immunity in OsteoarthritisR01AI081881 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI BRYAN, RU · 2009 to 2013
$1.7M
Innate Immunity in gouty InflammationR21AI067966 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI BRYAN, RU · 2007 to 2008
$377k
ATP-Citrate Lyase As A Novel Metabolic Target for OsteoarthritisI01BX002234 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI BRYAN, RU · 2015 to 2022
–
BLRD VA I01 BX002234NIAID NIH HHS AI-043477-12NIAID NIH HHS R01 AI043477NIAID NIH HHS R01 AI081881NIAID NIH HHS R21 AI067966NIAID NIH HHS R37 AI043477NIAMS NIH HHS AR-1067966NIEHS NIH HHS R01 ES006376
6 · The paper itself

Abstract

objectiveInterleukin-1beta (IL-1beta) is a key cytokine linked to the pathogenesis of acute arthritis. Caspase 1, neutrophil elastase, and chymase all process proIL-1beta to its biologically active form. This study was undertaken to examine the potential contributions of each of these proteases in experimental models of inflammatory arthritis.

methodsCaspase 1-deficient (Casp1-/-) and wild-type (WT) mice were tested for their response to arthritogenic K/BxN serum transfer for induction of arthritis or injection of monosodium urate monohydrate (MSU) crystals for induction of peritonitis. All mice were prophylactically treated with inhibitors of neutrophil elastase or chymase. Arthritic paws were tested for the presence of IL-1beta protein by enzyme-linked immunosorbent assay and Western blotting. Neutrophils and mast cells from WT and mutant mice were tested for their ability to secrete IL-1beta after in vitro stimulation, in the presence of protease inhibitors.

resultsCasp1-/- and WT mice developed paw swelling to the same extent in the K/BxN serum transfer-induced arthritis model. MSU crystal injection into Casp1-/- mice also resulted in neutrophil influx and production of measurable peritoneal IL-1beta protein. Both of these responses were attenuated with neutrophil elastase inhibitors. K/BxN serum transfer-induced arthritis was also reduced by treatment with a chymase inhibitor. Casp1-/- neutrophils and mast cells, when exposed to MSU crystals, secreted similar amounts of IL-1beta protein upon in vitro stimulation with lipopolysaccharide, albeit at lower levels than that secreted by WT cells. Elastase and chymase inhibitors reduced the amount of IL-1beta released by these cells.

conclusionThe production of IL-1beta by neutrophils and mast cells is not exclusively dependent on caspase 1, and other proteases can compensate for the loss of caspase 1 in vivo. These pathways might therefore compromise the caspase 1-targeted therapies in neutrophil-predominant arthritis.

Indexed as

AnimalsArthritis, ExperimentalAutoantibodiesCaspase 1Cells, CulturedChymasesEdemaEnzyme ActivationEnzyme InhibitorsGene SilencingHindlimbImmunization, PassiveInterleukin-1Interleukin-1betaJointsLeukocyte ElastaseAutoantibodiesCaspase 1ChymasesEnzyme InhibitorsInterleukin-1Interleukin-1betainterleukin 1 precursorLeukocyte ElastaseMyeloblastinProtein Precursors

Identifiers

PMID19950258
PMCPMC2847793
OpenAlexW1533217355

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.