Evidence map›Paper›PMID 32608058›Full record

ArticleBritish journal of pharmacology2020

Inhibition of Bruton's TK regulates macrophage NF-κB and NLRP3 inflammasome activation in metabolic inflammation.

Gareth S D Purvis, Massimo Collino, Haidee Aranda-Tavio, Fausto Chiazza, Caroline E O'Riordan, Lynda Zeboudj, Shireen Mohammad, Debora Collotta, Roberta Verta, Nicolas E S Guisot and 4 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 72 citations in OpenAlex.

  1. Review
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  4. Current and future landscape of Bruton tyrosine kinase inhibitors in allergy.The Journal of allergy and clinical immunology · 2025
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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

14 authors at 4 institutions in 2 countries.

Gareth S D PurvisWilliam Harvey Research Institute, Queen Mary University of London, London, UK.ORCID 0000-0003-4118-1568
Massimo CollinoDepartment of Drug Science and Technology, University of Turin, Turin, Italy.ORCID 0000-0001-8782-3496
Haidee Aranda-TavioSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Fausto ChiazzaDepartment of Drug Science and Technology, University of Turin, Turin, Italy.
Caroline E O'RiordanWilliam Harvey Research Institute, Queen Mary University of London, London, UK.
Lynda ZeboudjSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Shireen MohammadWilliam Harvey Research Institute, Queen Mary University of London, London, UK.
Debora CollottaDepartment of Drug Science and Technology, University of Turin, Turin, Italy.
Roberta VertaDepartment of Drug Science and Technology, University of Turin, Turin, Italy.
Nicolas E S GuisotRedx Pharma, Macclesfield, UK.
Peter BunyardRedx Pharma, Macclesfield, UK.
Magdi M YaqoobWilliam Harvey Research Institute, Queen Mary University of London, London, UK.
David R GreavesSir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID 0000-0003-2856-9410
Christoph ThiemermannWilliam Harvey Research Institute, Queen Mary University of London, London, UK.
Queen Mary University of London · GBUniversity of Turin · ITUniversity of Oxford · GBRedx Pharma (United Kingdom) · GB

Funding

Bart's and The London Charity Centre of Diabetic Kidney DiseaseBritish Heart Foundation FS/13/58/30648British Heart Foundation RG/15/10/23915British Heart Foundation RG/15/10/31485Oxford BHF Centre of Research Excellence RE/13/1/30181Queen Mary University of London to C.E.O. William Harvey Research Foundation
6 · The paper itself

Abstract

background and purposeThere are no medications currently available to treat metabolic inflammation. Bruton's tyrosine kinase (BTK) is highly expressed in monocytes and macrophages and regulates NF-κB and NLRP3 inflammasome activity; both propagate metabolic inflammation in diet-induced obesity. EXPERIMENTAL APPROACH: Using an in vivo model of chronic inflammation, high-fat diet (HFD) feeding, in male C57BL/6J mice and in vitro assays in primary murine and human macrophages, we investigated if ibrutinib, an FDA approved BTK inhibitor, may represent a novel anti-inflammatory medication to treat metabolic inflammation. KEY

resultsHFD-feeding was associated with increased BTK expression and activation, which was significantly correlated with monocyte/macrophage accumulation in the liver, adipose tissue, and kidney. Ibrutinib treatment to HFD-fed mice inhibited the activation of BTK and reduced monocyte/macrophage recruitment to the liver, adipose tissue, and kidney. Ibrutinib treatment to HFD-fed mice decreased the activation of NF-κB and the NLRP3 inflammasome. As a result, ibrutinib treated mice fed HFD had improved glycaemic control through restored signalling by the IRS-1/Akt/GSK-3β pathway, protecting mice against the development of hepatosteatosis and proteinuria. We show that BTK regulates NF-κB and the NLRP3 inflammasome specifically in primary murine and human macrophages, the in vivo cellular target of ibrutinib. CONCLUSION AND IMPLICATIONS: We provide "proof of concept" evidence that BTK is a novel therapeutic target for the treatment of diet-induced metabolic inflammation and ibrutinib may be a candidate for drug repurposing as an anti-inflammatory agent for the treatment of metabolic inflammation in T2D and microvascular disease.

Indexed as

InflammasomesNF-kappa BAnimalsGlycogen Synthase Kinase 3 betaInflammationMacrophagesMaleMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinGlycogen Synthase Kinase 3 betaInflammasomesNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseBruton's tyrosine kinasediabetesdrug repurposingmacrophagemetabolic inflammationNF-kBNLRP3

Identifiers

PMID32608058
PMCPMC7484557
OpenAlexW3039185763

What OpenQuestion holds

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LicenceCC BY
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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.