Kv1.3 Channel is Involved in Ox-LDL-induced Macrophage Inflammation Via ERK/NF-κB Signaling Pathway
Archives of Biochemistry and Biophysics(2022)
摘要
Macrophage inflammatory response is crucial for the initiation and progression of atherosclerosis. The voltage-gated potassium channel Kv1.3 plays an important role in the modulation of macrophage function. The aim of this study was to investigate the effect and possible mechanism of Kv1.3 on inflammation in oxidized low-density lipoprotein (ox-LDL)-induced RAW264.7 macrophages. Treatment with Kv1.3-siRNA attenuated the expression of IL-6 and TNF-α and reduced the phosphorylation of ERK1/2 and NF-κB in ox-LDL-induced macrophages. In contrast, overexpression of Kv1.3 with Lv-Kv1.3 promoted the expression of IL-6 and TNF-α, and increased ERK1/2 and NF-κB phosphorylation in macrophages. PD-98059, a specific inhibitor of ERK, reversed the expression of IL-6 and TNF-α in ox-LDL-treated macrophages. Kv1.3-siRNA did not inhibit inflammation any further when cells were treated with PD-98059. This suggests that ERK acts as a downstream regulator of the Kv1.3 channel. In conclusion, Kv1.3 may be an indispensable membrane protein in ox-LDL-induced RAW264.7 macrophage inflammation in atherosclerosis through the ERK/NF-κB pathway.
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关键词
Kv1,3 channel,Extracellular signal -regulated kinase,Nuclear factor,?B,Inflammation,Macrophage,Atherosclerosis
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