Low-Molecular-Weight Fucoidan Inhibits the Viability and Invasiveness and Triggers Apoptosis in IL-1[beta]-Treated Human Rheumatoid Arthritis Fibroblast Synoviocytes

Fucoidan is a sulfated polysaccharide found mainly in various species of brown algae and brown seaweed. Here, we investigated the effects of low-molecular-weight (LMW) fucoidan (4 kDa) on interleukin-1beta (IL-1[beta])-stimulated rheumatoid arthritis fibroblast-like synoviocyte (RAFLS). 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and annexin V/propidium iodide assay were used to assess cell viability and apoptosis, respectively. Transwell assay was performed to evaluate cell invasion. Reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay analysis was done to measure gene expression and secretion. Nuclear factor-kappa B (NF-[kappa]B) DNA binding activity was determined by electrophoretic mobility shift assay. LMW fucoidan dose-dependently inhibited the viability and induced apoptosis of IL-1[beta]-treated RAFLS. Fucoidan attenuated IL-1[beta]-induced invasion of RAFLS and decreased the expression and secretion of metalloproteinase (MMP)-1, MMP-3, and MMP-9. Fucoidan suppressed NF-[kappa]B binding activity, p65 nuclear translocation, and I[kappa]B-[alpha] degradation in IL-1[beta]-stimulated RAFLS. Additionally, IL-1[beta]-induced phosphorylation of p38 but not ERK or JNK was significantly impaired by fucoidan treatment. LMW fucoidan reduces the viability, survival, and invasiveness of IL-1[beta]-treated RAFLS, which is associated with inhibition of NF-[kappa]B and p38 activation. LMW fucoidan may have therapeutic potential in the treatment of rheumatoid arthritis.