Evidence map›Paper›PMID 29872077›Full record

ArticleScientific reports2018

MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice.

Agampodi Promoda Perera, Ruchira Fernando, Tanvi Shinde, Rohit Gundamaraju, Benjamin Southam, Sukhwinder Singh Sohal, Avril A B Robertson, Kate Schroder, Dale Kunde, Rajaraman Eri

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

174 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
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114 more citing papers are in PubMed but not listed here.

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

10 authors.

Agampodi Promoda PereraSchool of Health Sciences, University of Tasmania, Launceston, TAS, Australia. agampodi.perera@utas.edu.au.ORCID 0000-0002-3674-9940
Ruchira FernandoDepartment of Pathology, Launceston General Hospital, Launceston, TAS, Australia.
Tanvi ShindeSchool of Health Sciences, University of Tasmania, Launceston, TAS, Australia.
Rohit GundamarajuSchool of Health Sciences, University of Tasmania, Launceston, TAS, Australia.
Benjamin SouthamSchool of Health Sciences, University of Tasmania, Launceston, TAS, Australia.
Sukhwinder Singh SohalSchool of Health Sciences, University of Tasmania, Launceston, TAS, Australia.
Avril A B RobertsonInstitute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia.
Kate SchroderInstitute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia.
Dale KundeSchool of Health Sciences, University of Tasmania, Launceston, TAS, Australia.
Rajaraman EriSchool of Health Sciences, University of Tasmania, Launceston, TAS, Australia. rajaraman.eri@utas.edu.au.ORCID 0000-0003-1688-8043

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MCC950 a potent, highly specific small molecule inhibitor of canonical and noncanonical activation of NLRP3 inflammasome has been evaluated in a multitude of NLRP3 driven inflammatory diseases. However, the effect of MCC950 on colonic inflammation has not yet been reported. In the present study we investigated the effect of MCC950 in a spontaneous chronic colitis mouse model Winnie, which mimics human ulcerative colitis. Oral administration of 40 mg/kg MCC950 commencing at Winnie week seven for three weeks significantly improved body weight gain, colon length, colon weight to body weight ratio, disease activity index and histopathological scores. MCC950 significantly suppressed release of proinflammatory cytokines IL-1β, IL-18, IL1-α, IFNγ, TNF-α, IL6, IL17, chemokine MIP1a and Nitric Oxide in colonic explants. Moreover, MCC950 resulted in a significant decrease of IL-1β release and activation of caspase-1 in colonic explants and macrophage cells isolated from Winnie. Complete inhibition with MCC950 in Winnie colonic explants shows, for the first time, the contribution of inflammatory effects resulting exclusively from canonical and noncanonical NLRP3 inflammasome activation in colitis. Taken together, our results illustrate the efficacy of MCC950 in the treatment of murine ulcerative colitis and provides avenue for a potential novel therapeutic agent for human inflammatory bowel diseases.

Indexed as

Administration, OralAnimalsAnti-Inflammatory AgentsBody WeightColitisColonCytokinesDisease Models, AnimalEnzyme InhibitorsFuransHeterocyclic Compounds, 4 or More RingsHistocytochemistryIndenesInflammasomesInflammationMacrophagesAnti-Inflammatory AgentsCytokinesEnzyme InhibitorsFuransHeterocyclic Compounds, 4 or More RingsIndenesInflammasomesN-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamideNitric OxideNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReceptors, Cell SurfaceSulfonamidesSulfones

Identifiers

PMID29872077
PMCPMC5988655

What OpenQuestion holds

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LicenceCC BY
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.