New Hybrid FPR2 ligands enhance Hydrogen Sulfide release in primary microglia cultures following LPS-induced activation 9078

Abstract Description Hydrogen sulfide (H2S) is a novel regulator in neuroinflammation. However, its underlying molecular mechanism in the brain remains to be further elucidated. Recently we demonstrated that Formyl-Peptide Receptor 2 (FPR2) can mediate both pro-inflammatory and anti-inflammatory responses depending on the chemical structure of the ligand. Thus, we have developed an innovative class of hybrid ligands of the FPR2 exhibiting proresolving activity and able to modulate H2S release. We aimed to determine the pro-resolving effect of hybrid FPR2 agonist/H2S releaser compounds (Fz6, Fz9, and AMS) in primary microglial cell cultures. Primary cultures of glial cells were prepared from C57BL/6J mice. Fluorimetric detection of H2S generation by the use of WSP-1 dye was used. Fluorescence signal with a spectrofluorometer at λ ¼ 465/515 nm was read 1 hour after compound addition and 1,4,24 and 48 hours after lipopolysaccharide (LPS) treatment. Our results showed that only Fz6 was able to increase H2S release in microglial cell cultures. This effect was time-dependent and visible 24 and 48 hours after LPS stimulation. Moreover, Fz6 significantly reduced the pro-inflammatory mediators (IL-6, IL-1β) release, when microglial cells were stimulated with LPS. Our novel discoveries expanded the current understanding of the correlation between H2S and the pro-resolving role of FPR2 activation and opened new perspectives in the treatment of CNS disorders characterized by neuroinflammation. Funding Sources Supported by grant no. 2021/43/B/NZ4/01133, National Science Centre, Poland (Task 2). Topic Categories Neuroimmunology (NEUR)