H(2)S Donor SPRC Ameliorates Ischemic Stroke by Upregulating CD24.

BACKGROUND: Ischemic stroke is well-known for its high mortality and morbidity, but its treatment remains to be explored due to the current limitations. For example, severe neuroinflammation occurs after ischemic stroke; however, effective neuroinflammatory inhibitors are still lacking. Thus, the development of new therapeutic targets of inhibiting neuroinflammation is urgent. CD24 is a small heavy glycosylated protein, which plays a critical role in neural development and acts as an inflammatory suppressor in tumors and autoimmune diseases. But the role of CD24 in ischemic stroke remains unknown. AIMS: The role of CD24 in ischemic stroke should be explored. Additionally, the potential relationship between the H(2)S donor, S-propargyl-cysteine (SPRC) and CD24 in ischemic stroke should be revealed. METHODS: Mechanism studies have been performed both in vitro and in vivo to verify the CD24-mediated inflammation and migration. SPRC has been applied to treat ischemic stroke, and its potential association with CD24 has been studied. RESULTS: The overexpression of CD24 can inhibit the nuclear factor kappa B (NF-κB) inflammatory signaling pathway and promote the migration ability of M2 microglia cells via Src/Fak/Pyk2 signaling pathway in an inflammatory model of BV2 cells. SPRC can upregulate the level of endogenous H(2)S via cystathionase-β-synthase (CBS) and it indirectly plays a role in upregulating CD24. CONCLUSIONS: CD24 could be a potential target of inhibiting neuroinflammation. SPRC reduces inflammation in ischemic stroke by regulating the CD24/Iκ-Bα/NF-κB inflammatory signaling pathway and improves the migration ability of M2 microglia via CD24/Src/Fak/Pyk2 signaling pathway, which further alleviates the inflammatory response at the lesion.