Intra-articular injection of recombinant TRAIL induces synovial apoptosis and reduces inflammation in a rabbit knee model of arthritis

Arthritis Research & Therapy
Qingping YaoPaul D Robbins

Abstract

We demonstrated previously that local, intra-articular injection of an adenoviral vector expressing human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a rabbit knee model of inflammatory arthritis stimulated synovial apoptosis and reduced inflammation. To examine whether intra-articular injection of recombinant chimeric human TRAIL protein (rTRAIL) also induces apoptosis of proliferating rabbit synovium and reduces inflammation, we used an experimental rabbit arthritis model of rheumatoid arthritis, induced by intra-articular introduction of allogeneic fibroblasts genetically engineered to secrete human IL-1beta. Analysis of synovium isolated from the rabbits treated with intra-articular injection of rTRAIL, relative to saline control, showed areas of extensive acellular debris and large fibrous regions devoid of intact cells, similar to adenoviral mediated TRAIL gene transfer. Extensive apoptosis of the synovial lining was demonstrated using TUNEL analysis of the sections, corresponding to the microscopic findings in hematoxylin and eosin staining. In addition, leukocyte infiltration into the synovial fluid of the inflamed knee joints following rTRAIL treatment was reduced more than 50% compared with the ...Continue Reading

References

Jan 1, 1967·Annual Review of Medicine·V A Laine
Nov 1, 1993·European Journal of Nuclear Medicine·E DeutschK F Deutsch
May 31, 1996·The Journal of Biological Chemistry·R M PittiA Ashkenazi
Apr 4, 1997·Science·G PanV M Dixit
Oct 6, 1997·The EMBO Journal·H WalczakC T Rauch
Nov 5, 1997·The Journal of Biological Chemistry·M MacFarlaneE S Alnemri
Mar 4, 1998·European Journal of Immunology·I JeremiasK M Debatin
May 29, 1998·European Journal of Immunology·S M Mariani, P H Krammer
Jan 16, 1999·The Journal of Biological Chemistry·D W Seol, T R Billiar
Jun 16, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·Q YaoT J Oligino
Apr 17, 2003·Journal of the National Cancer Institute·Jean-Philippe HerbeuvalChristian Genin

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Citations

Jan 1, 2009·Mediators of Inflammation·Charles J Malemud
Oct 4, 2006·Arthritis Research & Therapy·Xin YouGary S Firestein
Mar 10, 2017·Nature Reviews. Rheumatology·Michael Croft, Richard M Siegel
Jan 15, 2015·Molecular Oncology·Zhenyu YaoDexian Zheng
May 28, 2010·Arthritis and Rheumatism·Luis Martinez-LostaoAlberto Anel
Nov 20, 2016·The FEBS Journal·Daniela SiegmundHarald Wajant
Jan 1, 2013·Clinical and Experimental Medicine·Anna NeveFrancesco Paolo Cantatore
Nov 26, 2009·The Journal of Pharmacology and Experimental Therapeutics·Cheng-Hao JinKang Choon Lee
Mar 16, 2011·Clinical and Experimental Immunology·D S Vinay, B S Kwon
Jul 29, 2015·Clinical and Experimental Pharmacology & Physiology·Honghai XuYuelin Zhang
Mar 27, 2020·Cellular & Molecular Immunology·I-Tsu Chyuan, Ping-Ning Hsu
Jan 11, 2012·Biochemical Pharmacology·Luis Martinez-LostaoJavier Naval

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Methods Mentioned

BETA
PCR
phosphotransferase
ELISA
lavage

Software Mentioned

Opera

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis