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Article

IL-6 trans-Signaling Impairs Sprouting Angiogenesis by Inhibiting Migration, Proliferation and Tube Formation of Human Endothelial Cells

1
Cardiovascular Research Center, School of Medical Sciences, Örebro University Södra Grev Rosengatan 32, 703 62 Örebro, Sweden
2
Department of Biomedical and Clinical Sciences (BKV), Division of Inflammation and Infection (II), Linköping University Campus US, 581 85 Linköping, Sweden
*
Author to whom correspondence should be addressed.
Cells 2020, 9(6), 1414; https://doi.org/10.3390/cells9061414
Received: 5 May 2020 / Revised: 27 May 2020 / Accepted: 4 June 2020 / Published: 5 June 2020
Sprouting angiogenesis is the formation of new capillaries from existing vessels in response to tissue hypoxia due to growth/development, repair/healing, and also chronic inflammation. In this study, we aimed to elucidate the effect of IL-6, a pleiotropic cytokine with both pro-inflammatory and anti-inflammatory functions, in regulating the sprouting angiogenic response of endothelial cells (ECs). We found that activation of IL-6 trans-signaling inhibited the migration, proliferation, and tube formation ability of ECs. In addition, inhibition of the autocrine IL-6 classic-signaling by depleting endogenous IL-6 from ECs impaired their tube formation ability. At the molecular level, we found that IL-6 trans-signaling in ECs upregulated established endogenous anti-angiogenic factors such as CXCL10 and SERPINF1 while at the same time downregulated known endogenous pro-angiogenic factors such as cKIT and CXCL8. Furthermore, prior activation of ECs by IL-6 trans-signaling alters their response to vascular endothelial growth factor-A (VEGF-A), causing an increased p38, but decreased Erk1/2 phosphorylation. Collectively, our data demonstrated the dual facets of IL-6 in regulating the sprouting angiogenic function of ECs. In addition, we shed light on molecular mechanisms behind the IL-6 trans-signaling mediated impairment of endothelial sprouting angiogenic response. View Full-Text
Keywords: VEGF-A signaling; neoangiogenesis; cytokine; Matrigel; HUVECs; IPA VEGF-A signaling; neoangiogenesis; cytokine; Matrigel; HUVECs; IPA
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MDPI and ACS Style

Zegeye, M.M.; Andersson, B.; Sirsjö, A.; Ljungberg, L.U. IL-6 trans-Signaling Impairs Sprouting Angiogenesis by Inhibiting Migration, Proliferation and Tube Formation of Human Endothelial Cells. Cells 2020, 9, 1414. https://doi.org/10.3390/cells9061414

AMA Style

Zegeye MM, Andersson B, Sirsjö A, Ljungberg LU. IL-6 trans-Signaling Impairs Sprouting Angiogenesis by Inhibiting Migration, Proliferation and Tube Formation of Human Endothelial Cells. Cells. 2020; 9(6):1414. https://doi.org/10.3390/cells9061414

Chicago/Turabian Style

Zegeye, Mulugeta M., Blanka Andersson, Allan Sirsjö, and Liza U. Ljungberg 2020. "IL-6 trans-Signaling Impairs Sprouting Angiogenesis by Inhibiting Migration, Proliferation and Tube Formation of Human Endothelial Cells" Cells 9, no. 6: 1414. https://doi.org/10.3390/cells9061414

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