Pharmacological targeting of the TLR8/AP-1 axis ameliorates scleroderma skin inflammation and fibrosis by suppressing monocyte-mediated endothelial injury - PubMed
3 hours ago
- #Systemic Sclerosis
- #Monocytes
- #TLR8/AP-1 axis
- TLR8 is significantly upregulated in monocytes of systemic sclerosis (SSc) patients and correlates with vascular symptoms like Raynaud's phenomenon.
- Activation of TLR8 via agonist VTX-2337 in monocytes promotes inflammatory cytokines and adhesion molecules through AP-1, leading to endothelial damage and transition to mesenchymal cells.
- Inhibition of AP-1 with T5224 blocks monocyte-mediated endothelial injury in vitro and reduces skin inflammation and fibrosis in a mouse model of SSc.
- Targeting the TLR8/AP-1 axis offers a potential therapeutic approach for treating scleroderma by disrupting harmful interactions between monocytes and endothelial cells.