Modulation of innate inflammation by therapeutic peptide P140 in a murine model of gout
MASTRIPPOLITO D. 1, GEORGEL P. 3, MULLER S. 1,2
1 CNRS UMR7242, Biotechnology and Cell Signaling/Strasbourg Drug Discovery and Development Institute (IMS), University of Strasbourg, Strasbourg, France; 2 Institute for Advanced Study, University of Strasbourg, Strasbourg, France; 3 ImmunoRhumatologie Moléculaire, UMR_S 1109, INSERM, University of Strasbourg, Strasbourg, France
Objectives Gout is a painful form of inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in the joints. With its prevalence rising sharply in recent decades, affecting 1-2% of the adult population worldwide, gout has become a significant healthcare concern. Current therapies are not universally effective, particularly in patients with long-standing hyperuricemia. Therefore, there is a need for novel therapeutic approaches to improve existing strategies and provide additional treatment possibilities for gout patients. This study aimed to evaluate the effect of the therapeutic peptide P140, an autophagy regulator, on innate inflammation in a murine model of gout. The objective was to determine whether P140 could attenuate inflammation and alleviate associated gout symptoms.
Methods A classic model of gout was induced in mice by injecting MSU crystals into the knee joint. Following gout induction, mice were treated with the P140 peptide. Inflammatory parameters, including neutrophil influx, pro-inflammatory cytokine production, and hypernociception, were assessed. In vitro analyses were conducted to investigate the mechanisms of P140 on neutrophils.
Results Treatment with the P140 peptide significantly decreased neutrophil influx into the knee joint and reduced pro-inflammatory cytokine production in mice. Furthermore, P140 administration resulted in a significant reduction in hypernociception. In vitro analyses demonstrated that P140 modulated neutrophil activity by enhancing apoptosis pathways and reducing NFκB phosphorylation. P140 also increased the production of annexin A1, a pro-resolving mediator.
Conclusion Our findings highlight the significant beneficial effect of the therapeutic peptide P140 in a murine model of neutrophilic inflammation in gout. These results suggest that P140 holds promise as a therapeutic strategy to mitigate inflammation and alleviate symptoms associated with gouty arthritis. Moreover, these findings underscore the importance of modulating innate inflammation using the therapeutic peptide P140, opening the way for further research on its potential application in other inflammatory conditions.