Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune joint disease that causes cartilage and bone damage or even disability, seriously endangering human health. Chronic synovial inflammation has been shown to play a vital role in disease sustainability. Therefore, downregulation of synovial inflammation is considered to be an effective discipline for RA therapy. Polyene phosphatidylcholine (PPC) is a hepatoprotective agent, which was observed to inhibit inflammation in macrophages and prevent collagen-induced arthritis (CIA) of rats in our previous study. However, the underlying mechanism remains unclear. The present study further reported that PPC can inhibit synovial inflammation. In lipopolysaccharide (LPS)-stimulated primary synovial fibroblasts (SFs) of mice, PPC significantly decreased pro-inflammatory cytokines production while increasing anti-inflammatory cytokines level. In this process, PPC downregulated the expression of TLR-2 and their downstream signaling molecules such as MyD88, p-ERK1/2, p-JNK1/2, and p-P38 in MAPK pathway and p-IκBα and NF-κB-p65 in NF-κB pathway. Moreover, the inhibitory effect of PPC on the above molecules and cytokines was weakened after pre-treatment with TLR-2 agonist Pam3CSK4. In addition, PPC lost its anti-inflammatory effect and its suppressing capabilityon MAPK and NF-κB pathways in TLR-2-/- primary SFs after exposure to LPS. Collectively, this study demonstrated that PPC can alleviate synovial inflammation through TLR-2-mediated MAPK and NF-κB pathways, which can be proposed to be a potential drug candidate for RA prevention.
Highlights
Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease in the world, affecting about 1% of the population
We previously reported that PPC can effectively improve the condition of collagen-induced arthritis (CIA) in rats [33], providing a new option for RA intervention therapy
In view of the vital role of synovial fibroblasts (SFs) inflammation in the pathogenesis of RA, we speculated that PPC plays the protective effect on CIA through inhibiting SFs inflammation
Summary
Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease in the world, affecting about 1% of the population. There are a variety of cells in the affected articular cavity, including synovial fibroblasts (SFs) and immune cells, cooperatively contributing to joint inflammation and bone destruction [4]. SFs represent one of the leading hyperplastic cells [5]. They produce chemokines and cytokines through the perception of dangerous molecules in the joints, to participate in the malignant inflammatory cycle [6, 7]. SFs can stimulate synovial vascularization through the release of proangiogenic factors, thereby promoting disease progression [8,9,10]. Down-regulation of synovial inflammation is regarded to be a key discipline for the treatment of RA [11]
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