IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression
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IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression. / Nielsen, Sebastian Rune; Hammer, Troels; Gibson, Josefine; Pepper, Michael S; Nisato, Riccardo E; Dissing, Steen; Tritsaris, Katerina.
I: Microcirculation, Bind 20, Nr. 6, 08.2013, s. 555-564.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression
AU - Nielsen, Sebastian Rune
AU - Hammer, Troels
AU - Gibson, Josefine
AU - Pepper, Michael S
AU - Nisato, Riccardo E
AU - Dissing, Steen
AU - Tritsaris, Katerina
N1 - © 2013 John Wiley & Sons Ltd.
PY - 2013/8
Y1 - 2013/8
N2 - 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 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. RESULTS: 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, were profoundly up-regulated upon IL-27 stimulation, and recombinant CXCL10 and CXCL11 inhibited FGF-2-induced proliferation in vitro. siRNA targeting of STAT1 almost completely abrogated CXCL10 and CXCL11 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 STAT1 activation. © 2013 John Wiley & Sons Ltd.
AB - 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 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. RESULTS: 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, were profoundly up-regulated upon IL-27 stimulation, and recombinant CXCL10 and CXCL11 inhibited FGF-2-induced proliferation in vitro. siRNA targeting of STAT1 almost completely abrogated CXCL10 and CXCL11 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 STAT1 activation. © 2013 John Wiley & Sons Ltd.
U2 - 10.1111/micc.12055
DO - 10.1111/micc.12055
M3 - Journal article
C2 - 23452095
VL - 20
SP - 555
EP - 564
JO - Microcirculation
JF - Microcirculation
SN - 1073-9688
IS - 6
ER -
ID: 47454949