IL-17A-associated PTGS2 and MMP9 inflammatory signaling in ischemic stroke: clinical correlation and experimental evidence.

BACKGROUND

IL-17A is implicated in post-stroke inflammation, but its downstream inflammatory mediators in ischemic stroke remain incompletely defined. This study investigated whether IL-17A-associated signaling is linked to PTGS2 and MMP9 expression in ischemic stroke and whether IL-17A neutralization modulates these changes after cerebral ischemia.

METHODS

Three GEO datasets were analyzed to identify candidate genes and enriched pathways. Serum IL-17A, PTGS2, and MMP9 levels were measured by ELISA in patients with acute ischemic stroke and controls, and their associations with admission National Institutes of Health Stroke Scale (NIHSS) scores were examined. A rat middle cerebral artery occlusion (MCAO) model was established, and IL-17A neutralizing antibody treatment was used to assess effects on inflammatory markers, neurological deficits, and infarct volume.

RESULTS

Bioinformatics analysis prioritized PTGS2 and MMP9 as candidate inflammatory genes enriched in the IL-17 signaling pathway. Serum IL-17A, PTGS2, and MMP9 levels were significantly elevated in patients with ischemic stroke versus controls (all P < 0.001). IL-17A was positively correlated with PTGS2 (rho = 0.292, P < 0.01), MMP9 (rho = 0.216, P < 0.05), and admission NIHSS score. In MCAO rats, IL-17A, PTGS2, and MMP9 expression increased together with PGE2 and IL-6 levels. IL-17A neutralizing antibody treatment was associated with reduced PTGS2 and MMP9 expression, lower PGE2 and IL-6 levels, decreased infarct volume, and improved neurological deficit scores in MCAO rats, although an isotype-matched IgG control was not included.

CONCLUSION

These findings support an IL-17A-associated PTGS2/MMP9 inflammatory network in ischemic stroke and suggest that IL-17A-associated inflammatory signaling may represent a biologically relevant pathway in post-ischemic injury, warranting further validation in studies incorporating appropriate isotype-matched antibody controls.