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Article

Pleiotropic, Unique and Shared Responses Elicited by IL-6 Family Cytokines in Human Vascular Endothelial Cells

by
Madelene Lindkvist
,
Mulugeta M. Zegeye
,
Magnus Grenegård
and
Liza U. Ljungberg
*
Cardiovascular Research Centre (CVRC), School of Medical Sciences, Örebro University, 70362 Örebro, Sweden
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(3), 1448; https://doi.org/10.3390/ijms23031448
Submission received: 20 December 2021 / Revised: 18 January 2022 / Accepted: 20 January 2022 / Published: 27 January 2022
(This article belongs to the Special Issue Advances in Endothelial Cell Biology)

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.
Keywords: cardiotrophin-1 (CT-1); ciliary neurotrophic factor (CNTF); CCL23; chemotaxis; interleukin-11 (IL-11); leukemia inhibitory factor (LIF); hepatocyte growth factor (HGF) cardiotrophin-1 (CT-1); ciliary neurotrophic factor (CNTF); CCL23; chemotaxis; interleukin-11 (IL-11); leukemia inhibitory factor (LIF); hepatocyte growth factor (HGF)

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MDPI and ACS Style

Lindkvist, M.; Zegeye, M.M.; Grenegård, M.; Ljungberg, L.U. Pleiotropic, Unique and Shared Responses Elicited by IL-6 Family Cytokines in Human Vascular Endothelial Cells. Int. J. Mol. Sci. 2022, 23, 1448. https://doi.org/10.3390/ijms23031448

AMA Style

Lindkvist M, Zegeye MM, Grenegård M, Ljungberg LU. Pleiotropic, Unique and Shared Responses Elicited by IL-6 Family Cytokines in Human Vascular Endothelial Cells. International Journal of Molecular Sciences. 2022; 23(3):1448. https://doi.org/10.3390/ijms23031448

Chicago/Turabian Style

Lindkvist, Madelene, Mulugeta M. Zegeye, Magnus Grenegård, and Liza U. Ljungberg. 2022. "Pleiotropic, Unique and Shared Responses Elicited by IL-6 Family Cytokines in Human Vascular Endothelial Cells" International Journal of Molecular Sciences 23, no. 3: 1448. https://doi.org/10.3390/ijms23031448

APA Style

Lindkvist, M., Zegeye, M. M., Grenegård, M., & Ljungberg, L. U. (2022). Pleiotropic, Unique and Shared Responses Elicited by IL-6 Family Cytokines in Human Vascular Endothelial Cells. International Journal of Molecular Sciences, 23(3), 1448. https://doi.org/10.3390/ijms23031448

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