TLR4‐induced upregulation of NALP3 is associated with increased caspase‐1 activity in human aortic endothelial cells

Previously, we reported a three‐tier model for inflammasome expression and inflammation privilege. According to the mRNA expression level of inflammasome components, vascular tissues are characterized as being in the second‐tier stand‐by status for inflammasome activation, indicating that these tissues do not express all inflammasome components constitutively. Based on our newly model, we hypothesized that a transcriptional regulation of inflammasome components genes is essential for inflammasome activation in vascular cells. To evaluate our hypothesis, we examined the mRNA expression levels of the main components of Nalp3 inflammasome including ASC, caspase‐1, IL‐1β, and Nalp3 in human aortic endothelial cells (HAECs). The expression levels of ASC, caspase‐1, and IL‐1β are relative high compared with Nalp3. After treatment with Toll‐like receptor (TLR) 4 agonist, lipopolysaccharide (LPS), for 24 hours, all the expression levels of those genes were up‐regulated. Of note, Nalp3, whose expression level is low during static condition, is the most sensitive one to LPS stimulation. In addition, treatment with LPS caused a slight increase in caspases‐1 activity. Together, our findings suggest that LPS can up‐regulate Nalp3 inflammasome components in transcriptional level which then leads to caspase‐1 activation in HAECs. This research was supported by NIH funding.