Oxaliplatin retains HMGB1 intranuclearly and ameliorates collagen type II-induced arthritis

Arthritis Research & Therapy
Therese OstbergU Andersson

Abstract

High mobility group box chromosomal protein 1 (HMGB1) is a nuclear protein that acts as a pro-inflammatory mediator following extracellular release. The protein is aberrantly expressed extracellularly in the settings of clinical and experimental synovitis. Therapy based on HMGB1 antagonists has shown encouraging results in experimental arthritis and warrants further scientific exploration using independent methods. In the present study we asked whether nuclear sequestration of HMGB1 preventing HMGB1 release would be beneficial for synovitis treatment. Oxaliplatin-based therapy was evaluated in collagen type II-induced arthritis in DBA/1 mice by clinical scoring and immunostaining of articular tissue. Oxaliplatin is an antineoplastic platinum-based compound that generates DNA adducts which tightly bind HMGB1. Secretion and intracellular location of HMGB1 were assessed by a novel HMGB1-specific ELISPOT assay and immunofluorescent staining. Intraperitoneal injections of oxaliplatin in early collagen type II-induced arthritis trapped HMGB1 with a distinct biphasic response pattern. Oxaliplatin therapy showed beneficial results for approximately 1 week. Microscopic evaluation of synovitis during this period showed strong nuclear HMG...Continue Reading

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Citations

Jul 5, 2008·Arthritis Research & Therapy·David S PisetskyUlf Andersson
Apr 14, 2010·Molecular Medicine·Hanna SchierbeckHelena Erlandsson Harris
Jan 5, 2011·Frontiers in Bioscience (Scholar Edition)·Zheng Zhou, Wen-Cheng Xiong
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Oct 16, 2012·European Journal of Pharmacology·Chao WangQuan Gong
Aug 30, 2016·Cellular & Molecular Immunology·Damien Bertheloot, Eicke Latz
Oct 21, 2016·Nature Reviews. Rheumatology·Meriam NeflaClaire Jacques
Nov 17, 2011·Journal of Innate Immunity·Michael T Lotze
Sep 16, 2014·Molecular Medicine·Nilesh M Agalave, Camilla I Svensson
Dec 20, 2012·Current Opinion in Rheumatology·Fleur SchaperJohanna Westra
Jun 27, 2019·Advances in Rheumatology·Marcos Tadeu Parron FernandesRegina Célia Poli-Frederico
Jan 9, 2021·Journal of Immunotherapy·Carolina Mendonça GorgulhoMichael T Lotze
Aug 3, 2020·Life Sciences·Ishnoor KaurSandeep Arora

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Methods Mentioned

BETA
acetylation

Software Mentioned

Elispot

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