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IL‐20 causes tube formation and spheroid sprouting in human lymphatic endothelial cells
Author(s) -
Dissing Steen,
Hammer Troels,
Ditlev Sisse B,
Hübschmann Martin V,
Hansen Anker J,
Tritsaris Katerina
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.964.20
Subject(s) - matrigel , microbiology and biotechnology , lymphatic system , spheroid , chemistry , protein kinase b , cytokine , lymphatic endothelium , pi3k/akt/mtor pathway , lymphangiogenesis , vascular endothelial growth factor c , endothelial stem cell , biology , cell , vascular endothelial growth factor , signal transduction , vascular endothelial growth factor a , immunology , cancer research , in vitro , vegf receptors , biochemistry , genetics , cancer , metastasis
IL‐20 is an arteriogenic cytokine that remodels collateral networks in vivo and in particular plays a role in cellular organization (Tritsaris et al., PNAS, 104, 15364–15369, 2007). We investigated its role in lymphangiogenesis using an immortalized lymphatic endothelial cell line, hTERT‐HDLEC, that express lymphatic markers and responds to VEGF‐C by forming tube like structures in matrigel. Upon stimulation of hTERT‐HDLEC with IL‐20 we found a rapid, transient increase in the intracellular, free Ca2+ concentration which was also observed with VEGF‐A but not with VEGF‐C. We also found that IL‐20 activates Akt and Erk1/2 phosphorylations within 10–60 minutes. In addition, the mTOR complex which is regulated by Akt signaling was phosphorylated within 5–30 min. In matrigels IL‐20 caused tube formations as well as morphological changes resulting in elongated cell structures. We inserted hTERT‐HDLEC into a collagen bed with 2 % FCS and found that both IL‐20 and VEGF‐C caused formation of spheroid sprouting within 24 hrs. These data show that IL‐20 activates signaling processes underlying changes in morphology and cell proliferation. Thus, IL‐20 is a cytokine that has the potential of activating or modulating the formation of lymphatic vessels. Its role in vivo could be in concert with other lymphangiogenic factors such as VEGF‐C and PDGF‐BB.