Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis

Date
2015-04
Language
American English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
Elsevier
Abstract

Dual-specificity phosphatase 2 (Dusp2; also called phosphatase of activated cells 1, PAC1) is highly expressed in activated immune cells. We examined whether a potential inhibitor of Dusp2, salubrinal, prevents inflammatory cytokine expression in immune cells and arthritic responses in a mouse model of anti-collagen antibody-induced arthritis (CAIA). Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). In this study, we examined the effects of salubrinal on expression of inflammation linked genes as well as a family of DUSP genes using genome-wide microarrays, qPCR, and RNA interference. We also evaluated the effects of salubrinal on arthritic responses in CAIA mice using clinical and histological scores. The results revealed that salubrinal decreased inflammatory gene expression in macrophages, T lymphocytes, and mast cells. Dusp2 was suppressed by salubrinal in LPS-activated macrophages as well as PMA/ionomycin-activated T lymphocytes and mast cells. Furthermore, a partial silencing of Dusp2 downregulated IL1β and Cox2, and the inflammatory signs of CAIA mice were significantly suppressed by salubrinal. Collectively, this study presents a novel therapeutic possibility of salubrinal for inflammatory arthritis such as RA through inhibition of Dusp2.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Hamamura, K., Nishimura, A., Chen, A., Takigawa, S., Sudo, A., & Yokota, H. (2015). Salubrinal Acts as a Dusp2 Inhibitor and Suppresses Inflammation in Anti-Collagen Antibody-Induced Arthritis. Cellular Signalling, 27(4), 828–835. http://doi.org/10.1016/j.cellsig.2015.01.010
ISSN
1873-3913
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Cellular Signalling
Source
PMC
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Author's manuscript
Full Text Available at
This item is under embargo {{howLong}}