Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease

In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically,in vitro, andin vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, includingPKM2 andGSDMD, was significantly upregulated and that the secretion of IL-1 β significantly increased.In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs ’ metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages.In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.
Source: Frontiers of Medicine - Category: General Medicine Source Type: research