부산대학교 도서관

Although interleukin-33 (IL-33), a member of (he IL-1 cytokine family, plays proinflammatory roles in immune cells as an 'alarmin.' little is known regarding the biological actions of IL-33 on vascular endothelial cells. To investigate the effects of IL-33 on vascular endothelial cells, we first screened the IL-33-regulated proteins in human umbilical vein endothelial cells (HUVECs) using a dot blot array and observed that IL-33 markedly increased growth-regulated oncogene-[alpha] (GRO-[alpha]), a chemokine that is also known as chemokine (C-X-C motif) ligand 1 (CXCL1). Real-time reverse transcription PCR and ELISA demonstrated that IL-33 induced GRO-[alpha] expression and secretion in HUVECs in a dose- and a time-dependent manner. Western immunoblot assay revealed that IL-33 activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N[H.sub.2]-terminal kinase (JNK). In addition, translocation of nuclear factor-[kappa]B (NF-[kappa]B) p65 to the nucleus of HUVECs was observed by IL-33 stimulation. Furthermore, treatment with pharmacological inhibitors against ERK1/2 (PD98059), JNK (SP600125). or NF-[kappa]B (BAY11-7085) significantly suppressed IL-33-induced GRO-[alpha] gene expression and secretion from HUVECs. Moreover, immunohistochemical staining demonstrated that IL-33 and GRO-[alpha] coexpressed in the endothelium of human carotid atherosclerotic plaque. Taken together, the present study indicates that IL-33 localized in the human atherosclerotic plaque increases GRO-[alpha] mRNA expression and protein secretion via activation of ERK1/2. JNK. and NF-[kappa]B in HUVECs. suggesting that IL-33 plays an important role in the pathophysiology and development of atherosclerosis. interleukin-33; growth-regulated oncogene-[alpha]/chemokine (C-X-C motif) ligand 1; endothelial cells; atherosclerosis doi: 10.1152/ajpregu.00435.2016.