1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol ameliorates arthritic joints through reducing neutrophil infiltration mediated by IL-6/STAT3 and MIP-2 activation

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Title
1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol ameliorates arthritic joints through reducing neutrophil infiltration mediated by IL-6/STAT3 and MIP-2 activation
Author(s)
Young-Jun Kim; Jae Min Shin; Su-Hyun Shin; J H Kim; K Y Sohn; H J Kim; J K Kang; S Y Yoon; Jae Wha Kim
Bibliographic Citation
Oncotarget, vol. 8, no. 57, pp. 96636-96648
Publication Year
2017
Abstract
The pathogenesis of rheumatoid arthritis (RA) has been implicated neutrophil extracellular traps (NETs) formation which could generate autoantigen. Neutrophil contributes to initiate and maintain the inflammatory process in the joint. In this study, we show that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) decreases neutrophil migration by regulating the activity of STAT3, a regulator of IL-6 and MIP-2 expression. PLAG caused a decrease in IL-6 production in the RAW264.7 macrophage cell line and in rheumatoid arthritis-fibroblast-like synoviocytes via the regulation of STAT3 signaling without affecting NF-κB signaling. In a mouse model of collagen-induced arthritis (CIA), arthritic symptoms were recapitulated, with increased IL-6 level in the synovium, and PLAG treatment restored IL-6 to a level comparable to that achieved with commercial therapeutics (such as Remicade or methotrexate). Staining of joint tissue with neutrophil-specific antibody showed that PLAG significantly reduced the infiltration of neutrophils into the joint synovium of CIA mice. The inhibitory effect of PLAG on IL-6/STAT3 or MIP-2 signaling also reduced the migration of differentiated neutrophils in vitro. Therefore, PLAG inhibits the infiltration of destructive neutrophils into inflammatory sites, and can be utilized as a potent therapeutic agent for the treatment of sustained inflammation and joint destruction
Keyword
Collagen-induced arthritisIL-6Immune responseImmunityImmunology and Microbiology SectionNeutrophilPLAGSTAT3
ISSN
1949-2553
Publisher
Impact Journals
DOI
http://dx.doi.org/10.18632/oncotarget.19384
Type
Article
Appears in Collections:
Division of Biomaterials Research > Cell Factory Research Center > 1. Journal Articles
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