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

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 in ammation has been shown to play a vital role in the disease sustainability. Therefore, down-regulation of synovial in ammation is considered to be an effective discipline for RA therapy. Polyene phosphatidylcholine (PPC) is a hepatoprotective agent, which was observed to inhibit in ammation 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 the synovial in ammation. In lipopolysaccharide (LPS)-stimulated primary synovial broblasts (SFs) of mice, PPC signi cantly decreased pro-in ammatory cytokines production while increasing anti-in ammatory cytokines level. In this process, PPC down-regulated the expression of TLR-2 and their downstream signaling molecules such as MyD88, p-ERK1/2, p-JNK1/2, p-P38 in the MAPK pathway and p-IκBα and NF-κB-p65 in NF-kB pathway. Moreover, the inhibitory effect of PPC on the above molecules and cytokines was weakened after the use of TLR-2 agonist Pam3CSK4. However, PPC lost its anti-in ammatory effect and showed an activation of MAPK and NF-kB pathways in the TLR-2 -/primary SFs after exposure to LPS. Furthermore, these results were con rmed in the SFs from the CIA mouse ex vivo. Collectively, this study demonstrated that PPC can alleviate synovial in ammation through TLR-2 mediated MAPK and NF-κB pathways, which can be proposed to be a potential drug candidate for RA therapy.

TNFAIP3 interacting protein 2 relieves lipopolysaccharide (LPS)‐induced inflammatory injury in endometritis by inhibiting NF‐kappaB activation

“…Xu et al revealed that Polyene Phosphatidylcholine prevented synovial inflammation via inactivation of NF-κB signaling. 38 Ma et al demonstrated that NF-κBp65 was involved in the mechanism of Jinzhen on novel SARS-Cov-2. 39 Yang et al demonstrated that the NF-κB pathway was related to Thioredoxin-1 mediates neuroprotection of Schisanhenol in SH-SY5Y cells.…”

“…There is growing evidence that the NF‐κB signal pathway plays a critical role in human disease. Xu et al revealed that Polyene Phosphatidylcholine prevented synovial inflammation via inactivation of NF‐κB signaling 38 . Ma et al demonstrated that NF‐κBp65 was involved in the mechanism of Jinzhen on novel SARS‐Cov‐2 39 .…”

MyD88 and Its Inhibitors in Cancer: Prospects and Challenges

“…Additionally, Astragaloside IV, Xiang Lin pills, berberine, and fluoxetine can inhibit the TLR4/MyD88/NF-κB signals, thereby exerting the effects of acute myocardial infarction, colitis, and ischemia-reperfusion injury, and relieve postoperative cognitive dysfunction and neuroinflammation in elderly mice [67][68][69][70][71][72][73][74][75][76][77][78][79][80]. Polyene phosphatidylcholine, a wellknown hepatoprotective drug, has also recently been found to act on the TLR2/MyD88 signaling pathway, inhibiting the binding of MyD88 and TLR, and activating the IκB kinase (IKK) complex to alleviate synovial inflammation [81]. In addition, studies have reported that pioglitazone can reduce oxidative stress through the TLR4/MyD88/NF-κB signaling pathway, thereby ameliorating the testicular toxic side effects of cisplatin treatment [75].…”

Regulation of macrophage polarization by targeted metabolic reprogramming for the treatment of lupus nephritis

“…This thus inhibits M1 and promotes M2 activation in macrophages. Additionally, the interaction between PPC and TLR-2 can suppress the release of pro-inflammatory cytokines (TNF-a, IL-6) and promote the production of anti-inflammatory cytokines (IL-10, TGF-β) in macrophages, thereby promoting macrophage polarization toward M2 and alleviating the symptoms of rheumatoid arthritis (Pan et al 2017 ; Xu et al 2022b ). Considering that LN is an immune-related disease similar to rheumatoid arthritis, PPC may be potentially used for the future treatment of LN.…”