Logo image
Back
A store-operated calcium channel inhibitor attenuates collagen-induced arthritis
Journal article   Open access   Peer reviewed

A store-operated calcium channel inhibitor attenuates collagen-induced arthritis

X H Gao, R Gao, Y Z Tian, P McGonigle, J E Barrett, Y Dai and H Hu
British journal of pharmacology, v 172(12), pp 2991-3002
Jun 2015
DOI: https://doi.org/10.1111/bph.13104
PMID: 25651822
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1111/bph.13104View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Anilides - administration & dosage Anilides - pharmacology Animals Arthritis, Experimental - pathology Arthritis, Experimental - prevention & control Arthritis, Rheumatoid - pathology Arthritis, Rheumatoid - prevention & control Calcium Channel Blockers - administration & dosage Calcium Channel Blockers - pharmacology Collagen - toxicity Cytokines - metabolism Dose-Response Relationship, Drug Inflammation - pathology Inflammation - prevention & control Male Mice Mice, Inbred DBA Pain - drug therapy Pain - etiology Thiadiazoles - administration & dosage Thiadiazoles - pharmacology
Store-operated calcium (SOC) channels are thought to play a critical role in immune responses, inflammatory diseases and chronic pain. The aim of this study was to explore the potential role and mechanisms of SOC channels in collagen-induced arthritis (CIA). The CIA mouse model was used to examine the effects of the SOC channel inhibitor YM-58483 on CIA and arthritic pain. Hargreaves' and von Frey hair tests were conducted to measure thermal and mechanical sensitivities of hind paws. elisa was performed to measure cytokine production, and haematoxylin and eosin staining was used to assess knee histological changes. Western blot analysis was performed to examine protein levels. Pretreatment with 5 or 10 mg · kg(-1) of YM-58483 reduced the incidence of CIA, prevented the development of inflammation and pain hypersensitivity and other signs and features of arthritis disease. Similarly, treatment with YM-58483 after the onset of CIA: (i) reversed the clinical scores; (ii) reduced paw oedema; (iii) attenuated mechanical and thermal hypersensitivity; (iv) improved spontaneous motor activity; (v) decreased periphery production of IL-1β, IL-6 and TNF-α; and (vi) reduced spinal activation of ERK and calmodulin-dependent PKII (CaMKIIα). This study provides the first evidence that inhibition of SOC entry prevents and relieves rheumatoid arthritis (RA) and arthritic pain. These effects are probably mediated by a reduction in cytokine levels in the periphery and activation of ERK and CaMKIIα in the spinal cord. These results suggest that SOC channels are potential drug targets for the treatment of RA.

Metrics

20 Record Views
33 citations in Web of Science
34 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Pharmacology & Pharmacy
Logo image