Astrocyte elevated gene-1 promotes inflammation and invasion of fibroblast-like synoviocytes in rheumatoid arthritis

• Published in: Tissue & cell 2017-12, Vol.49 (6), p.672-679
• Main Authors: Hong, Ruilong, Wang, Kun, Shi, Hongguang
• Format: Article
• Language: English
• Subjects: Adult; Aged; AKT protein; Arthritis; Arthritis, Rheumatoid - pathology; Astrocyte elevated gene-1; Attenuation; Cell Adhesion Molecules - metabolism; Cell Movement - physiology; Cytokines; Cytoplasm; Female; Fibroblasts - metabolism; Fibroblasts - pathology; Gene expression; Genes; HIV; Human immunodeficiency virus; Humans; Immunohistochemistry; Immunoprecipitation; Inflammation; Inflammation - metabolism; Inflammation - pathology; Interleukin 6; Invasion; Male; Middle Aged; Migration; NF-κB protein; Patients; Phosphorylation; Proteins; Rheumatoid arthritis; Ribonucleic acid; RNA; RNA-mediated interference; Staining; Synoviocytes; Synoviocytes - metabolism; Synoviocytes - pathology; Time dependence; Tumor necrosis factor-α
• ISSN: 0040-8166; 1532-3072
• DOI: 10.1016/j.tice.2017.09.005

•We provided the first demonstration that the expression and localization of AEG-1 in RA.•AEG-1 could promote the release of inflammatory mediators and the invasion of fibroblast-like synoviocytes.•3.AEG-1 may be a novel therapeutic target for RA. Astrocyte elevated gene-1 (AEG-1) was initially induced by HIV-1 infection and involved in tumor progression, migration and invasion as a nuclear factor-κB (NF-κB)-dependent gene. The present study we intended to investigate the protein expression of AEG-1 significantly associated with rheumatoid arthritis. Western blot analysis and immunohistochemistry demonstrated that AEG-1 was upregulated in synovial tissue of RA patients compared with the controls. Double immunofluorescent staining suggested that AEG-1 was expressed in fibroblast-like synoviocytes (FLS) of RA patients. Furthermore, the expression of AEG-1 in FLS was increased in time-dependent manner by TNF-α stimulation. Upon TNF-α-treated FLS, AEG-1 transferred from the cytoplasm to nucleus where it interacted with the p65 subunit of NF-κB, as examined by immunoprecipitation and immunofluorescent staining assay. Moreover, the inhibition of AEG-1 by RNA interference significantly suppressed TNF-α-induced IL-6 and MMP-3 expression, leading to attenuation of FLS migration and invasion and markedly decreased the phosphorylation of P65 and IκBα, as well as AKT in FLS. Collectively, Our findings provided evidence that AEG-1 contributed to the production of inflammatory cytokines, migration and invasion of RA FLS, and underscored the importance of AEG-1 in the inflammation process of RA.