IL-11 Suppresses VEGFR2 Expression and Hampers Endothelial Cell’s Wound Healing

Authors

  • V. Rodineliussen Stockholm University, Stockholm, Sweden
  • A. Waghmare Strathclyde institute of pharmacy and biomedical sciences, Glasgow, UK
  • R. Gustafsson Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden

DOI:

https://doi.org/10.15407/microbiolj86.04.086

Keywords:

endothelial cell, interleukin-6, interleukin-11, cytomegalovirus, wound healing, VEGFR2

Abstract

Endothelial cells (EC) line the lumen of all blood vessels and are crucial for vascular integrity, haemeostasis, and inflammation. EC are also targets for infections such as human cytomegalovirus (hCMV), which can induce vascular injury and release of various cytokines including the closely related interleukin (IL) - 11 and IL-6. Objective. To assess the effect of IL-11 and IL-6 on wound healing by EC. Methods. We report a follow-up study of our previous work on IL-11 and IL-6 responses to hCMV where the EC’s wound healing capacity and expression of relevant gene transcripts in EC treated with IL-11 or IL-6 are assessed. Results. Treatment with IL-11, but not with IL-6, hampered the wound healing capacity, and this effect may be due to suppression of VEGF signaling caused by suppression of VEGFR2. The VEGFA levels remained unaltered. Conclusions. IL-11 hampers the regenerating wound healing capacity of EC, and this may be due to the reduced expression of VEGFR2.

Downloads

Download data is not yet available.

References

Alarifi, S., Alkahtani, S., Al-Qahtani, A. A., Stournaras, C., & Sourvinos, G. (2020). Induction of interleukin-11 mediated by RhoA GTPase during human cytomegalovirus lytic infection. Cellular signalling, 70, 109599. https://doi.org/10.1016/j.cellsig.2020.109599

Clement, M., & Humphreys, I. R. (2019). Cytokine-Mediated Induction and Regulation of Tissue Damage During Cytomegalovirus Infection. Frontiers in immunology, 10, 78. https://doi.org/10.3389/fimmu.2019.00078

Cooke, B. M., Usami, S., Perry, I., & Nash, G. B. (1993). A simplified method for culture of endothelial cells and analysis of adhesion of blood cells under conditions of flow. Microvascular research, 45(1), 33–45. https://doi.org/10.1006/mvre.1993.1004

Gustafsson, R. K. L., Jeffery, H. C., Yaiw, K. C., Wilhelmi, V., Kostopoulou, O. N., Davoudi, B., Rahbar, A., Benard, M., Renné, T., Söderberg-Nauclér, C., & Butler, L. M. (2015). Direct infection of primary endothelial cells with human cytomegalovirus prevents angiogenesis and migration. The Journal of general virology, 96(12), 3598–3612. https://doi.org/10.1099/jgv.0.000301

Gustafsson, K. L. R., Renné, T., Söderberg-Naucler, C., & Butler, L. M. (2018). Human cytomegalovirus replication induces endothelial cell interleukin-11. Cytokine, 111, 563–566. https://doi.org/10.1016/j.cyto.2018.05.018

Jarvis, M. A., & Nelson, J. A. (2007). Human cytomegalovirus tropism for endothelial cells: not all endothelial cells are created equal. Journal of virology, 81(5), 2095–2101. https://doi.org/10.1128/JVI.01422-06

Jeffery, H. C., Söderberg-Naucler, C., & Butler, L. M. (2013). Human cytomegalovirus induces a biphasic inflammatory response in primary endothelial cells. Journal of virology, 87(11), 6530–6535. https://doi.org/10.1128/JVI.00265-13

Mahboubi, K., Li, F., Plescia, J., Kirkiles-Smith, N. C., Mesri, M., Du, Y., Carroll, J. M., Elias, J. A., Altieri, D. C., & Pober, J. S. (2001). Interleukin-11 up-regulates survivin expression in endothelial cells through a signal transducer and activator of transcription-3 pathway. Laboratory investigation; a journal of technical methods and pathology, 81(3), 327–334. https://doi.org/10.1038/labinvest.3780241

Nishina, T., Komazawa-Sakon, S., Yanaka, S., Piao, X., Zheng, D. M., Piao, J. H., Kojima, Y., Yamashina, S., Sano, E., Putoczki, T., Doi, T., Ueno, T., Ezaki, J., Ushio, H., Ernst, M., Tsumoto, K., Okumura, K., & Nakano, H. (2012). Interleukin-11 links oxidative stress and compensatory proliferation. Science signaling, 5(207), 5. https://doi.org/10.1126/scisignal.2002056

Nishina, T., Deguchi, Y., Kawauchi, M., Xiyu, C., Yamazaki, S., Mikami, T., & Nakano, H. (2023). Interleukin 11 confers resistance to dextran sulfate sodium-induced colitis in mice. Science, 26(2), 105934. https://doi.org/10.1016/j.isci.2023.105934

Pate, M., Damarla, V., Chi, D. S., Negi, S., & Krishnaswamy, G. (2010). Endothelial cell biology: role in the inflammatory response. Advances in clinical chemistry, 52, 109–130. https://doi.org/10.1016/S0065-2423(10)52004-3

Putoczki, T., & Ernst, M. (2010). More than a sidekick: the IL-6 family cytokine IL-11 links inflammation to cancer. Journal of leukocyte biology, 88(6), 1109–1117. https://doi.org/10.1189/jlb.0410226

Ribatti, D., Tamma, R., & Annese, T. (2021). The role of vascular niche and endothelial cells in organogenesis and regeneration. Experimental cell research, 398(1), 112398. https://doi.org/10.1016/j.yexcr.2020.112398

Santos, S. C., Miguel, C., Domingues, I., Calado, A., Zhu, Z., Wu, Y., & Dias, S. (2007). VEGF and VEGFR-2 (KDR) internalization is required for endothelial recovery during wound healing. Experimental cell research, 313(8), 1561–1574. https://doi.org/10.1016/j.yexcr.2007.02.020

Styles, J. N., Converse, R. R., Griffin, S. M., Wade, T. J., Klein, E., Nylander-French, L. A., Stewart, J. R., Sams, E., Hudgens, E., & Egorov, A. I. (2020). Human Cytomegalovirus Infections Are Associated With Elevated Biomarkers of Vascular Injury. Frontiers in cellular and infection microbiology, 10, 334. https://doi.org/10.3389/fcimb.2020.00334

Zhang, Y., Li, Y., He, A., Wang, J., Zhang, P., Lei, B., Huang, Z., Zhang, L., Zhao, W., & Ma, X. (2023). Efficacy of recombinant human interleukin-11 in preventing and treating oral mucositis after chemotherapy for patients with acute leukemia. BMC oral health, 23(1), 476. https://doi.org/10.1186/s12903-023-03118-4

Downloads

Published

2024-09-03

Issue

Section

Short Communications

How to Cite

Rodineliussen, V., Waghmare, A., & Gustafsson, R. (2024). IL-11 Suppresses VEGFR2 Expression and Hampers Endothelial Cell’s Wound Healing. Mikrobiolohichnyi Zhurnal, 86(4), 86-90. https://doi.org/10.15407/microbiolj86.04.086