NeuroD1 Knockdown Alleviates LPS-induced BV2 Microglial Cell Mediated Neuroinflammation
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Microglia activation is a hallmark of the neuroinflammatory response and contributes to the progression of neurodegenerative diseases. Neurogenic differentiation factor 1 (NeuroD1) has recently emerged as a potential modulator of the immune function in the central nervous system. Nevertheless, its precise role in microglial-mediated neuroinflammation remains unclear. This study examined the effects of NeuroD1 knockdown on lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglial cells and their impact on neuronal viability. LPS stimulation upregulated NeuroD1 expression in BV2 cells and primary microglia. Silencing NeuroD1 using short hairpin RNA (shND1) effectively suppressed LPS-induced expression. ND1 knockdown using shRNA attenuated the production of key proinflammatory cytokines, including TNF-α and IL-6, and inhibited the phosphorylation of JNK and ERK. Moreover, shND1 reduced NLRP3 inflammasome activation, as evidenced by the decreased levels of NLRP3, cleaved caspase-1, and IL-1β, and also diminished COX-2 expression. In a co-culture system of LPS-stimulated BV2 microglia and SH-SY5Y neuronal cells, a NeuroD1 deficiency in microglia alleviated LPS-induced neuronal apoptosis, as shown by the reduced Annexin V-positive populations and decreased cleaved caspase-3 expression. Collectively, these findings indicate that NeuroD1 plays a critical role in modulating the microglial inflammatory responses, suggesting that silencing it via shND1 may be a potential therapeutic strategy.
Abstract
Microglia activation is a hallmark of the neuroinflammatory response and contributes to the progression of neurodegenerative diseases. Neurogenic differentiation factor 1 (NeuroD1) has recently emerged as a potential modulator of the immune function in the central nervous system. Nevertheless, its precise role in microglial-mediated neuroinflammation remains unclear. This study examined the effects of NeuroD1 knockdown on lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglial cells and their impact on neuronal viability. LPS stimulation upregulated NeuroD1 expression in BV2 cells and primary microglia. Silencing NeuroD1 using short hairpin RNA (shND1) effectively suppressed LPS-induced expression. ND1 knockdown using shRNA attenuated the production of key proinflammatory cytokines, including TNF-α and IL-6, and inhibited the phosphorylation of JNK and ERK. Moreover, shND1 reduced NLRP3 inflammasome activation, as evidenced by the decreased levels of NLRP3, cleaved caspase-1, and IL-1β, and also diminished COX-2 expression. In a co-culture system of LPS-stimulated BV2 microglia and SH-SY5Y neuronal cells, a NeuroD1 deficiency in microglia alleviated LPS-induced neuronal apoptosis, as shown by the reduced Annexin V-positive populations and decreased cleaved caspase-3 expression. Collectively, these findings indicate that NeuroD1 plays a critical role in modulating the microglial inflammatory responses, suggesting that silencing it via shND1 may be a potential therapeutic strategy.