Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblastsReportar como inadecuado




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BMC Pharmacology

, 4:2

First Online: 17 February 2004Received: 21 October 2003Accepted: 17 February 2004

Abstract

BackgroundExtracts of Tripterygium wilfordii Hook F TWHF, a traditional Chinese herb, have been reported to show efficacy in patients with rheumatoid arthritis RA. Since RA is not only characterized by inflammation but also by synovial proliferation in the joints, we examined whether triptolide a constituent of TWHF could influence the proliferation of rheumatoid synovial fibroblasts RSF by induction of apoptosis.

ResultsRSF were obtained from RA patients during surgery and were treated with triptolide under various conditions. The viability and proliferation of RSF were measured by the 4-3-4-iodophenyl-2-4-nitrophenyl-2H-5-tetrazolio-1,3-benzene disulfonate WST-1 assay and by 5-bromo-2-deoxyuridine incorporation, respectively. Apoptosis was identified by detection of DNA fragmentation using an enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling TUNEL. The role of caspases in apoptosis of RSF was analyzed by measuring caspase-3 activity. Activation of the peroxisome proliferator-activated receptor PPAR γ was assessed by a luciferase reporter gene assay using RSF transfected with a plasmid containing the peroxisome proliferator response element. Triptolide decreased viability, inhibited proliferation, and induced apoptosis of RSF in a concentration-dependent manner at very low nM concentrations. Caspase-3 activity was increased by treatment with triptolide and was suppressed by caspase inhibitors. Although PPARγ activation was induced by 15-deoxy-Δ-prostaglandin J2, triptolide did not induce it under the same experimental conditions. An extract of TWHF also induced DNA fragmentation in RSF.

ConclusionThe mechanism of action remains to be studied; however, triptolide may possibly have a disease-modifying effect in patients with RA.

List of abbreviations usedRSFrheumatoid synovial fibroblasts

PPARγperoxisome proliferator-activated receptor γ

COXcyclooxygenase

PGprostaglandin

15dPGJ215-deoxy-Δ-PGJ2

FBSfetal bovine serum

IL-1βinterleukin-1β

NF-κBnuclear factor-kappaB

TNFtumor necrosis factor

TRAILTNF-related apoptosis inducing ligand

BrdU5-bromo-2-deoxyuridine

ELISAenzyme-linked immunosorbent assay

TUNELterminal deoxynucleotidyl transferase-mediated dUTP nick end labelling

PPREperoxisome proliferator response element.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2210-4-2 contains supplementary material, which is available to authorized users.

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Autor: Natsuko Kusunoki - Ryuta Yamazaki - Hidero Kitasato - Moroe Beppu - Haruhito Aoki - Shinichi Kawai

Fuente: https://link.springer.com/



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