Inhibition of NF-κB pathway in fibroblast-like synoviocytes by α-mangostin implicated in protective effects on joints in rats suffering from adjuvant-induced arthritis
| Autor: | Lin-Ming Lu, Qin Yin, Jian Zuo, Guo-Dong Wang, Yan Li, Jiajie Luan, Zhan-Gang Xiao, Yu-Wei Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Xanthones T cell Interleukin-1beta Immunology Population Anti-Inflammatory Agents Arthritis Apoptosis Pharmacology T-Lymphocytes Regulatory Arthritis Rheumatoid Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Immune system In vivo medicine Animals Humans Immunology and Allergy education Cells Cultured Cell Proliferation education.field_of_study Hyperplasia Tumor Necrosis Factor-alpha Chemistry Synovial Membrane NF-kappa B FOXP3 Forkhead Transcription Factors NF-κB medicine.disease Arthritis Experimental Synoviocytes Rats 030104 developmental biology medicine.anatomical_structure Signal Transduction |
| Zdroj: | International Immunopharmacology. 56:78-89 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2018.01.016 |
| Popis: | α-Mangostin (MG) is a bioactive compound isolated from mangosteen. This study was aimed to investigate effects of MG on adjuvant-induced arthritis (AA) in rats and decipher the underlying mechanisms. Clinical severity of AA was evaluated by paw oedema, arthritis score, and hematological parameters. Digital radiography (DR) and histological examinations were employed to assess joints destructions. Immune functions were evaluated by T cell subsets distribution. Effects on NF-κB pathway were investigated by immunohistochemical, western-blot and immunofluorescence methods both in vivo and vitro . It was found MG possessed superior anti-inflammatory effects in vivo , suggested by attenuated paw swelling, reduced inflammatory cells infiltration and decreased the secretion of TNF-α and IL-1β in serum. Meanwhile MG inhibited fibrous hyperplasia, synovial angiogenesis, cartilage and bone degradation in AA rats. Although MG exerted little effects on CD4 + population, it greatly decreased IFN-γ positive cells and promoted expression of FOXP3 in immune organs, indicating restoration of Th1/Treg cells ratio and recovery of immune homeostasis in vivo . Inhibition of NF-κB induced by MG was indicated by reduced the expression of p-p65 and VEGF in synovium. In vitro experiments found MG at 10 μg/ml significantly suppressed the expression and phosphorylation of key proteins implicated in NF-κB pathway and inhibited nucleus translocation of p65. These changes led to increased apoptosis and proliferation inhibition of HFLS-RA cells. The results demonstrated regulation of immune functions was deeply involved in the therapeutic actions of MG on AA, and it's inhibition on NF-κB in fibroblast-like synoviocytes was associated to the protective effects on joints. |
| Databáze: | OpenAIRE |
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