3′‐Sialyllactose as an inhibitor of p65 phosphorylation ameliorates the progression of experimental rheumatoid arthritis

Abstract

Background and Purpose3′‐Sialyllactose (3′‐SL) is a safe compound that is present in high levels in human milk. Although it has anti‐inflammatory properties and supports immune homeostasis, its effect on collagen‐induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3′‐SL on the progression of rheumatoid arthritis (RA) in in vitro and in vivo models.Experimental ApproachThe anti‐arthritic effect of 3′‐SL was analysed with fibroblast‐like synoviocytes in vitro and an in vivo mouse model of CIA. RT‐PCR, Western blotting and ELISA were performed to evaluate its effects in vitro. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin‐O and haematoxylin staining.Key Results3′‐SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3′‐SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro‐inflammatory cytokines, https://en.wikipedia.org/wiki/Matrix_metalloproteinases and osteoclastogenesis via NF‐κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF‐κB signalling pathway, was totally blocked by 3′‐SL in the RA models.Conclusions and Implications3′‐SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated via blockade of the NF‐κB signalling pathway. Therefore, 3′‐SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA.

Alleviation of Synovial Inflammation of Juanbi-Tang on Collagen-Induced Arthritis and TNF-Tg Mice Model

“…P65 participates in the classical NF-kappa B pathway. The inhibition of p65 phosphorylation was proven to suppress the pathogenesis of RA (Roman-Blas and Jimenez, 2006;Kang et al, 2018), as JBT did in this study. In the meantime, the effect inhibiting p38-MAPK was found.…”

NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis

“…Cartilage destruction is a characteristic of RA, in which MMPs secreted by RA FLSs play an important role 21 . Therefore, we researched the effect of NR1D1 on the activation of MMP3 and MMP13.…”

Cirsium japonicum var. maackii and apigenin block Hif‐2α‐induced osteoarthritic cartilage destruction

“…In both clinical and experimental OA, cartilage destruction and inflammation are the final biological results of MMP activation and expression of ADAMTS and COX‐2 respectively . Upstream and downstream regulators of MMP and COX‐2 expression are known to be pro‐inflammatory cytokines (eg, IL‐1β, IL‐6, IL‐17 and TNF‐α) and transcription factors (eg, NF‐κB and HIF‐2α) respectively . Non‐steroidal anti‐inflammatory drugs are the most commonly prescribed medications for MMP, COX‐2 and NF‐κB regulation as well as OA treatment .…”

“…Pro-inflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α) were purchased from GenScript (Piscataway, NJ, USA). Mouse articular chondrocytes were treated with IL-1β (1 ng/mL), IL-6 (100 ng/mL), IL-17 (10 ng/ mL) or TNF-α (50 ng/mL) and co-treated with CJM extract (10,50 or 100 μg/mL), apigenin (10,25 or 50 μmol/L), cirsimarin (10, 25 or 50 μmol/L) or cirsimaritin (10,25 or 50 μmol/L) for 24 h before they were harvested.…”