eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank
vol. 15
Clinical research

Modulator role of infliximab and methotrexate through the transient receptor potential melastatin 2 (TRPM2) channel in neutrophils of patients with rheumatoid arthritis: a pilot study

Atalay Dogru
Mustafa Nazıroglu
Bilal Cig

Arch Med Sci 2019; 15 (6): 1415–1424
Online publish date: 2018/11/19
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease causing symmetric polyarthritis. In this study, we aimed to investigate the effects of infliximab (INF) and methotrexate (MTX) on apoptosis, oxidative stress, and calcium signaling in the neutrophils of RA patients.

Material and methods
Neutrophils were isolated from 10 patients with newly diagnosed RA and 10 healthy controls. They were divided into four groups (control, RA, RA + MTX, RA + INF) and incubated with MTX and INF. In the cell viability (MTT) test, the ideal non-toxic dose and incubation time of MTX were found to be 0.1 mM and 1 h, respectively. The neutrophils were also incubated with the TRPM2 channel blocker N-(p-amylcinnamoyl) anthranilic acid (ACA).

Intracellular free Ca2+ concentration, intracellular reactive oxygen species (ROS) production, mitochondrial depolarization, lipid peroxidation, apoptosis, and caspase 3 and caspase 9 activities were found to be significantly higher in the neutrophils of RA patients compared to controls. MTT, reduced glutathione (GSH) level, and glutathione peroxidase (GSHPx) activity were significantly lower in the neutrophils of RA patients. However, MTT, GSH and GSHPx values were detected to be significantly increased with INF and MTX therapies. The Ca2+ concentrations were further decreased by the ACA therapy.

Our results suggest that INF and MTX are useful antagonists in apoptosis and mitochondrial oxidative stress in the neutrophils of RA patients. INF and MTX decreased the Ca2+ concentration through inhibition of the TRPM2 channel in the neutrophils of RA patients. It may be a new pathway in the mechanisms of anti-rheumatic drugs.


apoptosis, oxidative stress, calcium signaling, transient receptor potential melastatin 2 channel, rheumatoid arthritis

Quick links
© 2020 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe