Dieckol ameliorates inflammatory response via inhibition of CHI3L1 expression in collagen-induced arthritis rats
Main Article Content
Keywords
chitinase-3-like protein-1, collagen-induced arthritis, Dieckol, inflammatory response
Abstract
Background: Dieckol (DEK), the main phlorotannin of brown algal, has been regarded as a powerful anti-inflammatory agent in various diseases. Rheumatoid arthritis (RA) is a typical inflammatory autoimmune disease affecting synovial joints. However, the pharmaceutical effect of DEK on RA is still waiting to be unveiled.
Methods: A collagen-induced arthritis (CIA) rat model was established and DEK was administered intraperitoneally for three weeks. Paw swelling and histologic analysis were performed to evaluate CIA progression. Inflammatory cytokine and oxidative biomarker expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Vascular endothelial growth factor A (VEGFA) expression in synovial joint was assessed by immunoblotting and immunofluorescent (IF) staining. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to evaluate chondrocyte apoptosis. Western blot assay was performed to determine the expression level of nuclear erythroid-derived 2-like 2 (Nrf2), chitinase 3-like protein 1(CHI3L1) and apoptosis-specific proteins. Finally, CHI3L1 overexpression was used to explore its essential role in the biological effect of DEK in vivo.
Results: DEK treatment significantly ameliorates paw swelling, inflammatory cell infiltration, chondrocyte apoptosis and vascular pannus formation in CIA rats. Moreover, inflammatory cytokine and oxidative biomarker expression was also attenuated by DEK treatment. Notably, DEK treatment obviously promoted Nrf2 nuclear import and CHI3L1 expression in synovial joint. Overexpression of CHI3L1 by AVV-mediated transfection abrogated the pharmaceutical effect of DEK in vivo.
Conclusion: This study provides a promising translational potential of DEK as an anti-rheumatic drug facilitating RA clinical treatment.
References
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