Polyene Phosphatidylcholine Interacting with TLR-2 Prevents the Synovial Inflammation via Inactivation of MAPK and NF-κB Pathways.

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 capability on 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. © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Zixuan Xu, Wenting Hao, Daxiang Xu, Yan He, Ziyi Yan, Fenfen Sun, Xiangyang Li, Xiaoying Yang, Yinghua Yu, Renxian Tang, Kuiyang Zheng, Wei Pan. Polyene Phosphatidylcholine Interacting with TLR-2 Prevents the Synovial Inflammation via Inactivation of MAPK and NF-κB Pathways. Inflammation. 2022 Aug;45(4):1507-1519

Mesh Tags

Substances

PMID: 35107766

search → result