Th2 cytokines inhibit lymphangiogenesis Journal Article
| Authors: | Savetsky, I. L.; Ghanta, S.; Gardenier, J. C.; Torrisi, J. S.; García Nores, G. D.; Hespe, G. E.; Nitti, M. D.; Kataru, R. P.; Mehrara, B. J. |
| Article Title: | Th2 cytokines inhibit lymphangiogenesis |
| Abstract: | Lymphangiogenesis is the process by which new lymphatic vessels grow in response to pathologic stimuli such as wound healing, inflammation, and tumor metastasis. It is well-recognized that growth factors and cytokines regulate lymphangiogenesis by promoting or inhibiting lymphatic endothelial cell (LEC) proliferation, migration and differentiation. Our group has shown that the expression of T-helper 2 (Th2) cytokines is markedly increased in lymphedema, and that these cytokines inhibit lymphatic function by increasing fibrosis and promoting changes in the extracellular matrix. However, while the evidence supporting a role for T cells and Th2 cytokines as negative regulators of lymphatic function is clear, the direct effects of Th2 cytokines on isolated LECs remains poorly understood. Using in vitro and in vivo studies, we show that physiologic doses of interleukin-4 (IL-4) and interleukin-13 (IL-13) have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration, and tubule formation. Inhibition of these cytokines with targeted monoclonal antibodies in the cornea suture model specifically increases inflammatory lymphangiogenesis without concomitant changes in angiogenesis. These findings suggest that manipulation of anti-lymphangiogenic pathways may represent a novel and potent means of improving lymphangiogenesis. © 2015 Savetsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | adult; controlled study; protein expression; unclassified drug; human cell; nonhuman; protein function; cell proliferation; mouse; animal tissue; cell survival; apoptosis; interleukin 13; interleukin 4; cell protein; animal experiment; animal model; in vivo study; in vitro study; monoclonal antibody; endothelium cell; extracellular matrix; lymphangiogenesis; lymphedema; th2 cell; cell isolation; cell migration; upregulation; lymphocyte function; recombinant interleukin 13; interleukin 4 receptor alpha; lymphatic endothelial cell; human; male; article; prox 1 protein; recombinant interleukin 4 |
| Journal Title: | PLoS ONE |
| Volume: | 10 |
| Issue: | 6 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2015-06-03 |
| Start Page: | e0126908 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0126908 |
| PROVIDER: | scopus |
| PMCID: | PMC4454507 |
| PUBMED: | 26039103 |
| DOI/URL: | |
| Notes: | Export Date: 3 August 2015 -- Source: Scopus |
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