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 alpha and IL-1 beta 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-kappa B p65 level at 6 hours but not at 2 hours. Cytokines induced a biphasic degradation of I kappa B alpha and 3-MA selectively blocked the late-phase I kappa B alpha degradation. Our results suggest that cytokine-induced autophagy contributes to late-phase I kappa B alpha degradation, facilitates NF-kappa 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.
Date:
2017-09
Relation:
Scientific Reports. 2017 Sep;7:Article number 12472.
