Diabetic retinopathy is a chronic, low-grade inflammatory disease. The present study aimed to investigate the effect of forkhead transcription factor O1 (FoxO1) expression on interleukin-1β (IL-1β)-induced autostimulation, both in vitro in human retina microvascular endothelial cells (HRMECs), and in vivo in retinas isolated from streptozotocin-induced diabetic rats. High-glucose (HG) and recombinant IL-1β treatment were both shown to increase the expression of FoxO1 and IL-1β in HRMECs in a dose-dependent manner. IL-1 receptor antagonist (IL-1RA) and mitogen-activated protein kinase (MAPK) inhibitors reduced IL-1β-induced expression of FoxO1 in HRMECs. Moreover, the increased expressions of FoxO1 and IL-1β in the retinas of diabetic rats were significantly decreased by intravitreal injection of lentiviral vector-mediated FoxO1 small-interfering RNA. Together, these results suggest that HG triggers IL-1β synthesis in HRMECs. The produced IL-1β induces increased FoxO1 expression, as well as interacts with the IL-1 receptor to activate MAPK signaling and thereby induces IL-1β autostimulation. The IL-1β-induced autostimulation can be inhibited by downregulation of FoxO1, accompanied by a reduction of inflammation. Together, these findings identify novel functions for FoxO1 and IL-1β in diabetic retinopathy.
Keywords: Autostimulation; Diabetic retinopathy; Forkhead transcription factor O1; Inflammation; Interleukin-1β.
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