Evidence map›Paper›PMID 36521376›Full record

ArticlePloS one2022

Therapeutic effect of ibrutinib, a selective Bruton's tyrosine kinase inhibitor, in orbital fibroblasts from patients with Graves' orbitopathy.

Hyun Young Park, Min Kyung Chae, JaeSang Ko, Don O Kikkawa, Sun Young Jang, Jin Sook Yoon

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

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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

6 authors at 3 institutions in 2 countries.

Hyun Young ParkDepartment of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.ORCID 0000-0002-1673-6392
Min Kyung ChaeDepartment of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
JaeSang KoDepartment of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Don O KikkawaDivision of Oculofacial Plastic and Reconstructive Surgery, Department of Ophthalmology, University of California San Diego, La Jolla, California, United States of America.
Sun Young JangDepartment of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.ORCID 0000-0002-4723-3712
Jin Sook YoonDepartment of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.ORCID 0000-0002-8751-9467
Yonsei University · KRSoonchunhyang University · KRUniversity of California San Diego · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeBruton's tyrosine kinase (BTK) is an essential protein in B-cell antigen receptor (BCR) signaling pathway and is known to be related to pathogenetic effect on B-cell related malignancies and various autoimmune diseases. In this study, we investigated the therapeutic effect of ibrutinib, an orally bioavailable BTK inhibitor in the pathogenesis of Graves' orbitopathy (GO) in in vitro model.

methodsExpression of BTK in orbital tissues from GO and normal control subjects were evaluated by real-time polymerase chain reaction (PCR). Primary cultured orbital fibroblasts from each subject were exposed to ibrutinib and stimulated with interleukin (IL)-1β or insulin like growth factor (IGF)-1. Production of inflammatory cytokines was evaluated by real time PCR and enzyme-linked immunosorbent assays (ELISA). The downstream transcription factors were also determined by western blot assays.

resultsThe expression of BTK in GO tissues were significantly higher than in healthy controls. After stimulation of GO orbital fibroblasts with IL-1β or IGF-1, BTK mRNA and phosphorylated (p)- BTK protein expression was also enhanced. Ibrutinib reduced the expression of BTK mRNA and proteins of p-BTK, and inhibited the IL-1β- and IGF-1-induced production of proinflammatory cytokines including IL-6, IL-8 and COX-2 in both GO and normal cells. Ibrutinib also significantly attenuated phosphorylation of Akt, p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) in IL-1β stimulated GO cells and Akt, JNK, and NF-κB in IL-1ß stimulated normal cells.

conclusionsBTK expression is enhanced in GO tissue and orbital fibroblasts. Ibrutinib, a BTK inhibitor suppresses proinflammatory cytokine production as well as phosphorylation of Akt and NF-κB protein. Our results suggest the potential role of BTK in GO inflammatory pathogenesis and possibility of a novel therapeutic target of GO.

Indexed as

Graves OphthalmopathyAdenineAgammaglobulinaemia Tyrosine KinaseCells, CulturedCytokinesFibroblastsHumansInsulin-Like Growth Factor INF-kappa BPiperidinesProto-Oncogene Proteins c-aktRNA, MessengerTyrosine Kinase InhibitorsAdenineAgammaglobulinaemia Tyrosine KinaseCytokinesibrutinibInsulin-Like Growth Factor INF-kappa BPiperidinesProto-Oncogene Proteins c-aktRNA, MessengerTyrosine Kinase Inhibitors

Identifiers

PMID36521376
PMCPMC9754806
OpenAlexW4311802094

What Socratic holds

Textmetadata
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 Socratic graph.