Abstract
Vascular endothelial cells express glycoprotein 130 (gp130), which is utilized as a signaling receptor by cytokines in the interleukin-6 (IL-6) family. Several IL-6 family cytokines can be found in the circulatory system during physiological or pathological conditions, and may influence endothelial function and response. This study evaluated and compared the cellular and molecular responses induced by IL-6 family cytokines in human endothelial cells. A proteomic analysis showed that IL-6 family cytokines induce the release of a range of proteins from endothelial cells, such as C-C motif chemokine ligand 23, hepatocyte growth factor, and IL-6. Pathway analysis indicated that gp130-signaling in endothelial cells regulates several functions related to angiogenesis and immune cell recruitment. The present investigation also disclosed differences and similarities between different IL-6 family cytokines in their ability to induce protein release and regulate gene expression and intracellular signaling, in regards to which oncostatin M showed the most pronounced effect. Further, this study showed that soluble gp130 preferentially blocks trans-signaling-induced responses, but does not affect responses induced by classic signaling. In conclusion, IL-6 family cytokines induce both specific and overlapping molecular responses in endothelial cells, and regulate genes and proteins involved in angiogenesis and immune cell recruitment.
Highlights
IntroductionThe vascular endothelium plays a crucial role in maintaining vascular homeostasis
The vascular endothelium plays a crucial role in maintaining vascular homeostasis.Due to their strategic location on the luminal side of all blood vessels, vascular endothelial cells are in constant contact with circulating blood, and are continuously exposed to numerous circulating mediators, such as cytokines and chemokines
The expression of receptors utilized by IL-6 family cytokines was evaluated in HUThe expression of receptors utilized by IL-6 family cytokines was evaluated in HUVECs using quantitative real-time PCR (qPCR)
Summary
The vascular endothelium plays a crucial role in maintaining vascular homeostasis Due to their strategic location on the luminal side of all blood vessels, vascular endothelial cells are in constant contact with circulating blood, and are continuously exposed to numerous circulating mediators, such as cytokines and chemokines. Cytokines are important signaling molecules, released into the blood and other tissues, that mediate their effect by binding to specific surface receptors. IL-6 family cytokines have been shown to affect the release of inflammatory mediators, the expression of adhesion molecules, migration, and proliferation [2,3]. The IL-6 family cytokines bind specific surface receptors (alpha receptors), which, upon binding, dimerize with gp130 to induce an intracellular signal [4] (Figure 1). In addition to the classic cytokine signaling induced via surface
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