Cytokine-induced autophagy promotes long-term VCAM-1 but not ICAM-1 expression by degrading late-phase IκBα.

ABSTRACT: Pro-inflammatory cytokines are known to induce endothelial cell autophagy, but the role of autophagy in regulating the expression of pro-inflammatory molecules has not been characterized. We hypothesized that autophagy facilitates expression of endothelial adhesion molecules. TNFα and IL-1β induced autophagy markers in human umbilical vein endothelial cells and inhibition of autophagy by 3-methyladenine (3-MA) blocked adhesion of Jurkat lymphocytes. Interestingly, 3-MA suppressed VCAM-1 but not ICAM-1 expression at 24 hours but not 6 hours. 3-MA suppressed VCAM-1 transcription and decreased nuclear NF-κB p65 level at 6 hours but not at 2 hours. Cytokines induced a biphasic degradation of IκBα and 3-MA selectively blocked the late-phase IκBα degradation. Our results suggest that cytokine-in

SUBMITTER: Chu LY 

PROVIDER: S-EPMC5622139 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature