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IL‐27 Inhibits Lymphatic Endothelial Cell Proliferation by STAT1‐Regulated Gene Expression
Author(s) -
Nielsen Sebastian Rune,
Hammer Troels,
Gibson Josefine,
Pepper Michael S.,
Nisato Riccardo E.,
Dissing Steen,
Tritsaris Katerina
Publication year - 2013
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12055
Subject(s) - chemokine , cell growth , microbiology and biotechnology , lymphatic endothelium , biology , angiogenesis , stat , endothelial stem cell , lymphatic system , signal transduction , stat3 , immune system , cancer research , immunology , in vitro , biochemistry , genetics
Objective 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. Methods IL ‐27‐stimulated signal transduction in human dermal lymphatic endothelial cells was measured by western blotting and synthesis of CXCL 10 and CXCL 11 by use of RT ‐ PCR and ELISA . Proliferation was measured using MTT and BrdU kits and the role of STAT 1 and chemokines was determined by use of si RNA and recombinant proteins. Results Stimulation of lymphatic endothelial cell cultures with IL ‐27 induced JAK dependent phosphorylation of STAT 1 and STAT 3 and inhibited lymphatic endothelial cell proliferation and migration. Expression of CXCL 10 and CXCL 11, both STAT 1 target genes, was profoundly up‐regulated upon IL ‐27 stimulation, and recombinant CXCL 10 and CXCL 11 inhibited FGF ‐2‐induced proliferation in vitro . si RNA targeting of STAT 1 almost completely abrogated CXCL 10 and CXCL 11 expression as well as the proliferative effect of IL ‐27. Conclusions IL ‐27 function as an anti‐lymphangiogenic regulator in vitro by up‐regulating chemokines and interfering with the mitogenic effect of growth factors through STAT 1 activation.