Proteasome inhibitor MG‐132 enhances the expression of interleukin‐6 in human umbilical vein endothelial cells: Involvement of MAP/ERK kinase

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Abstract
Interleukin‐6 (IL‐6) is a multifunctional cytokine that plays an important role in inflammatory reactions. We have addressed the possible regulation of IL‐6 expression by the ubiquitin‐protease system in human umbilical vein endothelial cells. Cultured endothelial cells were treated with MG‐132, a protease inhibitor, and the levels of IL‐6 mRNA and protein were measured by reverse transcription‐PCR and ELISA. MG‐132 increased the expression of IL‐6 mRNA and protein; and this effect was abolished by the pretreatment of the cells with U0126, an inhibitor of MAP or ERK kinases (MEK1/2). MG‐132 treatment was also found to enhance the level of phosphorylated MEK1/2. Treatment of the cells with actinomycin D inhibited IL‐6 expression in response to MG‐132, suggesting the transcriptional upregulation of IL‐6 under proteasomal inhibition. We conclude that a protease inhibitor MG‐132 upregulates IL‐6 expression in vascular endothelial cells, at least in part, through the activation of MEK1/2.
Funding Information
  • Aomori Bank