There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Atherosclerosis (AS) is a chronic inflammatory disease that is characterized by the
deposition of lipids in the vascular wall and the formation of foam cells. Macrophages
play a critical role in the development of this chronic inflammation. An increasing
amount of research shows that microRNAs affect many steps of inflammation. The goal
of our study was to investigate the regulatory effect of miR-181a on the NLRP3 inflammasome
pathway and explore its possible mechanism. Compared with the control group, the expression
of miR-181a was downregulated in the carotid tissue of AS group mice, while the expression
of MEK1 and NLRP3-related proteins was upregulated significantly. In vitro, when THP-1
macrophages were stimulated with oxidized low-density lipoprotein (ox-LDL), the expression
of miR-181a was decreased, the MEK/ERK/NF-κB inflammatory pathways were activated
and the expression of NLRP3 inflammasome-related proteins was upregulated. Exogenous
overexpression of miR-181a downregulated the activation of the MEK/ERK/NF-κB pathway
and decreased the expression of NLRP3 inflammasome-related proteins (such as NLRP3,
caspase-1, interleukin-18 [IL-18], IL-1β, etc). Exogenous miR-181a knockdown showed
the opposite results to those of overexpression group. A luciferase reporter assay
proved that miR-181a inhibited the expression of MEK1 by binding to its 3'-untranslated
region. When we knocked down miR-181a and then treated cells with U0126 before ox-LDL
stimulation, we found that U0126 reversed the increased activation of the MEK/ERK/NF-κB
pathway and upregulation of NLRP3 inflammasome-related proteins (NLRP3, caspase-1,
IL-18, IL-1β) that resulted from miR-181a knockdown. Our study suggests that miR-181a
regulates the activation of the NLRP3 inflammatory pathway by altering the activity
of the MEK/ERK/NF-κB pathway via targeting of MEK1.