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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Nov 20, 2015; 5(4): 225-231
Published online Nov 20, 2015. doi: 10.5493/wjem.v5.i4.225
Published online Nov 20, 2015. doi: 10.5493/wjem.v5.i4.225
Disease control by regulation of P-glycoprotein on lymphocytes in patients with rheumatoid arthritis
Shizuyo Tsujimura, Yoshiya Tanaka, the First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan
Author contributions: All the authors contributed to this paper.
Supported by In part by research Grants-In-Aid for Scientific Research by the Ministry of Health, Labor and Welfare of Japan; the Ministry of Education, Culture, Sports, Science and Technology of Japan; University of Occupational and Environmental Health, Japan.
Conflict-of-interest statement: Tanaka Y has received consulting fees, lecture fees, and/or honoraria from Abbvie, Chugai, Astellas, Takeda, Santen, Mitsubishi-Tanabe, Pfizer, Janssen, Eisai, Daiichi-Sankyo, UCB, GlaxoSmithKline, and Bristol-Myers, and has also received research grants from Mitsubishi-Tanabe, Chugai, MSD, Astellas, and Novartis; Dr. Tsujimura S declares no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yoshiya Tanaka, MD, PhD, Professor, the First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan. tanaka@med.uoeh-u.ac.jp
Telephone: +81-93-6031611 Fax: +81-93-6919334
Received: September 13, 2014
Peer-review started: September 13, 2014
First decision: September 28, 2014
Revised: March 7, 2015
Accepted: August 30, 2015
Article in press: August 31, 2015
Published online: November 20, 2015
Peer-review started: September 13, 2014
First decision: September 28, 2014
Revised: March 7, 2015
Accepted: August 30, 2015
Article in press: August 31, 2015
Published online: November 20, 2015
Core Tip
Core tip: In patients with refractory rheumatoid arthritis (RA) and high disease activity, overexpression of P-glycoprotein (P-gp) on lymphocytes can cause resistance to anti-rheumatic drugs through efflux of intracellular drugs from these cells. Lymphocytes activated by various stimuli, including tumor necrosis factor-α in RA patients apparently acquire P-gp-mediated multidrug resistance against certain anti-rheumatic drugs, which are substrates of P-gp. The use of biological agents that reduce P-gp expression as well as P-gp antagonists can successfully reduce the efflux of drugs from lymphocytes, suggesting that they can be used to overcome drug-resistance and improve clinical outcome.