Maresin1 ameliorates MSU crystal-induced inflammation by upregulating Prdx5 expression

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• Maresin1 (MaR1) is a lipid mediator with anti-inflammatory properties.
• MaR1 has shown potential in suppressing MSU crystal-induced inflammation.
• The precise molecular mechanisms of MaR1's action against MSU crystal inflammation are not fully understood.

Purpose of the Study:

• To investigate the molecular mechanism by which MaR1 inhibits MSU crystal-induced inflammation.
• To explore the role of Prdx5 in MaR1-mediated anti-inflammatory effects.
• To evaluate MaR1's therapeutic potential in gout models.

Main Methods:

• Macrophages were pretreated with MaR1 and stimulated with fatty acids (FAs) and MSU crystals (FAs+MSUc).
• In vivo studies assessed MaR1's effects on MSUc-induced peritonitis and arthritis models.
• Key signaling pathways, including Keap1-Nrf2 and AMPK, were analyzed.

Main Results:

• MaR1 suppressed MSU crystal-induced inflammation both in vitro and in vivo.
• MaR1 upregulated Prdx5 expression by regulating the Keap1-Nrf2 signaling axis.
• Prdx5 activation by MaR1 improved cellular homeostasis, reduced mitochondrial fragmentation, and protected against fatty acid oxidation defects.

Conclusions:

• MaR1 treatment attenuates MSU crystal-induced inflammation through Prdx5 upregulation.
• Prdx5 plays a critical role in MaR1's anti-inflammatory effects.
• This study suggests Prdx5 as a potential therapeutic target for preventing acute gout attacks.