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

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. TNF? and IL-1? 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-?B p65 level at 6?hours but not at 2?hours. Cytokines induced a biphasic degradation of I?B? and 3-MA selectively blocked the late-phase I?B? degradation. Our results suggest that cytokine-induced autophagy contributes to late-phase I?B? degradation, facilitates NF-?B nuclear translocation and VCAM-1 transcription for long-term VCAM-1 expression. With a cytokines array assay, we found that 3-MA also inhibited IP-10 expression. These findings provide new information about the role of endothelial autophagy in persistent expression of VCAM-1 and IP-10 which enhance lymphocyte recruitment and adhesion to endothelium.

SUBMITTER: Chu LY 

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

REPOSITORIES: biostudies-literature