Metformin or α-Lipoic Acid Attenuate Inflammatory Response and NLRP3 Inflammasome in BV-2 Microglial Cells
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Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease that can be described by the occurrence of dementia due to a decline in cognitive function. The disease is characterized by the formation of extracellular and intracellular amyloid plaques. Amyloid beta (Aβ) is a hallmark of AD, and microglia can be activated in the presence of Aβ. Activated microglia secrete pro-inflammatory cytokines. Furthermore, S100A9 is an important innate immunity pro-inflammatory contributor in inflammation and a potential contributor to AD. This study examined the effects of metformin and α-LA on the inflammatory response and NLRP3 inflammasome activation in Aβ- and S100A9-induced BV-2 microglial cells. Metformin and α-LA attenuated inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, metformin and α-LA inhibited the phosphorylation of JNK, ERK, and p38. They activated the nuclear factor kappa B (NF-κB) pathway and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Moreover, metformin and α-LA reduced the marker levels of the M1 phenotype, ICAM1, whereas the M2 phenotype, ARG1, was increased. These findings suggest that metformin and α-LA are therapeutic agents against the Aβ- and S100A9-induced neuroinflammatory responses.
Abstract
Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease that can be described by the occurrence of dementia due to a decline in cognitive function. The disease is characterized by the formation of extracellular and intracellular amyloid plaques. Amyloid beta (Aβ) is a hallmark of AD, and microglia can be activated in the presence of Aβ. Activated microglia secrete pro-inflammatory cytokines. Furthermore, S100A9 is an important innate immunity pro-inflammatory contributor in inflammation and a potential contributor to AD. This study examined the effects of metformin and α-LA on the inflammatory response and NLRP3 inflammasome activation in Aβ- and S100A9-induced BV-2 microglial cells. Metformin and α-LA attenuated inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, metformin and α-LA inhibited the phosphorylation of JNK, ERK, and p38. They activated the nuclear factor kappa B (NF-κB) pathway and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Moreover, metformin and α-LA reduced the marker levels of the M1 phenotype, ICAM1, whereas the M2 phenotype, ARG1, was increased. These findings suggest that metformin and α-LA are therapeutic agents against the Aβ- and S100A9-induced neuroinflammatory responses.
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