Ab0734 Peptidylarginine Deiminase 4 (Pad4) Inhibitor 4,6-Bis(2,2,2-Trifluoroethoxy)-1,3,5-Triazin-2-Amine Ii Ameliorates Collagen-Induced Arthritis in Mice

Background: Peptidylarginine deiminase-4 (PAD4) is a calcium-dependent enzyme that catalyzes the conversion of arginine into citrulline in macromolecules within the body. Dysregulated PAD4 plays a crucial role in the occurrence and development of Rheumatoid arthritis (RA). Therefore, PAD4 is considered a promising target for diagnosing and treating RA. Objectives: In this study, we explored for the first time the therapeutic potential of the PAD4 inhibitor known as 4,6-bis(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-amine, referred to as TTA, in collagen-induced arthritis. Methods: We immunized DBA/1 mice with type II collagen, and the TTA treatment commenced on the 21st day after induction. Throughout the treatment period, we closely monitored alterations in body weight, assessed paw swelling through clinical scoring, and conducted histological examinations of the joints. On the 42nd day, we further examined changes in inflammatory cytokines in the serum and analyzed shifts in T-cell subpopulations within lymphatic tissues using ELISA and flow cytometry techniques. Results: The findings revealed that TTA treatment could alleviate arthritis symptoms, with improvements observed in joint manifestations and histological damage. Additionally, lung histological staining and experimental analysis of the pro-inflammatory cytokine TNF-α indicated signs of improvement. Furthermore, intracellular staining analysis of the immune system within the inguinal lymph nodes and spleen suggested a reduction in Th17 cells. Conclusion: In summary, TTA effectively mitigated collagen-induced arthritis in mice, indicating its potential as a future therapeutic option for the treatment of rheumatoid arthritis. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.