IL‐27 Inhibits Lymphatic Endothelial Cell Proliferation by STAT1‐Regulated Gene Expression. (9th August 2013)

• Record Type: Journal Article
• Authors: Nielsen, Sebastian Rune; Hammer, Troels; Gibson, Josefine; Pepper, Michael S.; Nisato, Riccardo E.; Dissing, Steen; Tritsaris, Katerina
• Is Part Of: Microcirculation. Volume 20:Number 6(2013:Aug.)
• Page Start: 555
• Page End: 564
• Publication Date: 2013-08-09
• Subjects: Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12055
• Languages: English
• ISSNs: 1073-9688

Abstract

<abstract abstract-type="main" id="micc12055-abs-0001"> <title>Abstract</title> <sec id="micc12055-sec-0001" sec-type="section"> <title>Objective</title> <p>IL‐27 belongs to the IL‐12 family of cytokines and is recognized for its role in Th cell differentiation and as an inhibitor of tumor angiogenesis. The purpose of this study was to investigate the effect of IL‐27 on proliferation of lymphatic endothelial cells to gain insight into the interplay between the immune system and development of the lymphatic system.</p> </sec> <sec id="micc12055-sec-0002" sec-type="section"> <title>Methods</title> <p>IL‐27‐stimulated signal transduction in human dermal lymphatic endothelial cells was measured by western blotting and synthesis of CXCL10 and CXCL11 by use of RT‐PCR and ELISA. Proliferation was measured using MTT and BrdU kits and the role of STAT1 and chemokines was determined by use of siRNA and recombinant proteins.</p> </sec> <sec id="micc12055-sec-0003" sec-type="section"> <title>Results</title> <p>Stimulation of lymphatic endothelial cell cultures with IL‐27 induced JAK dependent phosphorylation of STAT1 and STAT3 and inhibited lymphatic endothelial cell proliferation and migration. Expression of CXCL10 and CXCL11, both STAT1 target genes, was profoundly up‐regulated upon IL‐27 stimulation, and recombinant CXCL10 and CXCL11 inhibited FGF‐2‐induced proliferation <italic>in vitro</italic>. siRNA targeting of STAT1 almost completely abrogated CXCL10 and CXCL11 expression as well as the proliferative effect of IL‐27.</p> </sec> <sec id="micc12055-sec-0004" sec-type="section"> <title>Conclusions</title> <p>IL‐27 function as an anti‐lymphangiogenic regulator <italic>in vitro</italic> by up‐regulating chemokines and interfering with the mitogenic effect of growth factors through STAT1 activation.</p> </sec> </abstract>