ArticleAngiogenesis2013
Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration.
Article in Angiogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Mechanisms and treatments of lymphedema.Frontiers in immunology · 2026Review
- IL-19 Is a Novel Lymphangiocrine Factor Inducing Lymphangiogenesis and Lymphatic Junctional Regulation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Review of treatment strategies after lymphadenectomy: From molecular therapeutics to immediate microsurgical lymphatic reconstruction.Journal of vascular surgery. Venous and lymphatic disorders · 2024Review
- Intestinal Lymphatic Dysfunction in Kidney Disease.Circulation research · 2023Review
- Therapeutic Lymphangiogenesis Is a Promising Strategy for Secondary Lymphedema.International journal of molecular sciences · 2023Review
- Radiation therapy attenuates lymphatic vessel repair by reducing VEGFR-3 signalling.Frontiers in pharmacology · 2023Article
- Effect of Human Synovial Fluid From Osteoarthritis Patients and Healthy Individuals on Lymphatic Contractile Activity.Journal of biomechanical engineering · 2022Article
- Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity.Metabolites · 2021Review
- Integrating Biological Advances Into the Clinical Management of Breast Cancer Related Lymphedema.Frontiers in oncology · 2020Review
- Immune cell trafficking, lymphatics and hypertension.British journal of pharmacology · 2019Review
- Inflammation and Lymphatic Function.Frontiers in immunology · 2019Review
- The Interplay Between Lymphatic Vessels and Chemokines.Frontiers in immunology · 2019Review
- Pterygium Pathology: A Prospective Case-Control Study on Tear Film Cytokine Levels.Mediators of inflammation · 2019Article
- Potential lymphangiogenesis therapies: Learning from current antiangiogenesis therapies-A review.Medicinal research reviews · 2018Review
- Multipotent Adult Progenitor Cells Support Lymphatic Regeneration at Multiple Anatomical Levels during Wound Healing and Lymphedema.Scientific reports · 2018Article
- The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis.Cellular and molecular gastroenterology and hepatology · 2016Review
- Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1.Lipids in health and disease · 2016Article
- The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production.Molecular and cellular biochemistry · 2015Article
- Interleukin-8: A potent promoter of human lymphatic endothelial cell growth in gastric cancer.Oncology reports · 2015Article
- Bridging the divide between pathogenesis and detection in lymphedema.Seminars in cell & developmental biology · 2015Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs. Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling. Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57(KIP2) by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis in vivo. Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis. Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis in vitro and in vivo with a therapeutic efficacy in post-surgical lymphedema.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.