Evidence map›Paper›PMID 19404960›Full record

ArticleArthritis and rheumatism2009

Down-regulation of myeloid cell leukemia 1 by epigallocatechin-3-gallate sensitizes rheumatoid arthritis synovial fibroblasts to tumor necrosis factor alpha-induced apoptosis.

Salahuddin Ahmed, Matthew D Silverman, Hubert Marotte, Kevin Kwan, Natalie Matuszczak, Alisa E Koch

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 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 22% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

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  8. Ursolic acid facilitates apoptosis in rheumatoid arthritis synovial fibroblasts by inducing SP1-mediated Noxa expression and proteasomal degradation of Mcl-1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018
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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 1 institution in 1 country.

Salahuddin AhmedDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA. salahmed@umich.edu
Matthew D Silverman
Hubert Marotte
Kevin Kwan
Natalie Matuszczak
Alisa E Koch
University of Michigan–Ann Arbor · US

Funding

IL-18 in rheumatoid inflammation and angiogenesisR01AR048267 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOCH, ALISA E · 2003 to 2007
$1.4M
IL 4 AND IL 13 GENE THERAPY FOR ARTHRITISR01AI040987 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOCH, ALISA E · 1998 to 2006
$1.3M
Inhibition of RA synovial fibroblasts invasion by green tea polyphenolsR21AT003633 · NCCIH · UNIVERSITY OF TOLEDO · PI AHMED, SALAH-UDDIN · 2007 to 2008
$376k
Inhibition of CCR1/CCR5 mediated angiogenesis and joint destruction by EGCGR03AR055741 · NIAMS · UNIVERSITY OF TOLEDO · PI AHMED, SALAH-UDDIN · 2008 to 2010
$223k
IL 4 AND IL 13 GENE THERAPY FOR ARTHRITISR21AI040987 · NIAID · NORTHWESTERN UNIVERSITY · PI KOCH, ALISA E · 1997 to 1997
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NCCIH NIH HHS AT-003633NCCIH NIH HHS R21 AT003633NIAID NIH HHS AI-40987NIAID NIH HHS R01 AI040987NIAMS NIH HHS AR-055741NIAMS NIH HHS AR-48267NIAMS NIH HHS R01 AR048267NIAMS NIH HHS R03 AR055741
6 · The paper itself

Abstract

objectiveOverexpression of the antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) in rheumatoid arthritis (RA) synovial fibroblasts is a major cause of their resistance to tumor necrosis factor alpha (TNFalpha)-induced apoptosis. This study was undertaken to evaluate the efficacy of epigallocatechin-3-gallate (EGCG) in down-regulating Mcl-1 expression and its mechanism of RA synovial fibroblast sensitization to TNFalpha-induced apoptosis.

methodsEGCG effects on cultured RA synovial fibroblast cell morphology, proliferation, and viability over 72 hours were determined by microscopy and a fluorescent cell enumeration assay. Caspase 3 activity was determined by a colorimetric assay. Western blotting was used to evaluate the apoptosis mediators poly(ADP-ribose) polymerase (PARP), Mcl-1, Bcl-2, Akt, and nuclear translocation of NF-kappaB.

resultsIn RA synovial fibroblasts, EGCG (5-50 microM) inhibited constitutive and TNFalpha-induced Mcl-1 protein expression in a concentration- and time-dependent manner (P<0.05). Importantly, EGCG specifically abrogated Mcl-1 expression in RA synovial fibroblasts and affected Mcl-1 expression to a lesser extent in osteoarthritis and normal synovial fibroblasts or endothelial cells. Inhibition of Mcl-1 by EGCG triggered caspase 3 activity in RA synovial fibroblasts, which was mediated via down-regulation of the TNFalpha-induced Akt and NF-kappaB pathways. Caspase 3 activation by EGCG also suppressed RA synovial fibroblast growth, and this effect was mimicked by Akt and NF-kappaB inhibitors. Interestingly, Mcl-1 degradation by EGCG sensitized RA synovial fibroblasts to TNFalpha-induced PARP cleavage and apoptotic cell death.

conclusionOur findings indicate that EGCG itself induces apoptosis and further sensitizes RA synovial fibroblasts to TNFalpha-induced apoptosis by specifically blocking Mcl-1 expression and, hence, may be of promising adjunct therapeutic value in regulating the invasive growth of synovial fibroblasts in RA.

Indexed as

Anticarcinogenic AgentsApoptosisArthritis, RheumatoidBlotting, WesternCaspase 3CatechinCells, CulturedCell SurvivalDown-RegulationFibroblastsMyeloid Cell Leukemia Sequence 1 ProteinOsteoarthritisProto-Oncogene Proteins c-bcl-2Synovial MembraneTumor Necrosis Factor-alphaAnticarcinogenic AgentsCaspase 3Catechinepigallocatechin gallateMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2Tumor Necrosis Factor-alpha

Identifiers

PMID19404960
PMCPMC2917979
OpenAlexW2095076141

What OpenQuestion holds

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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.