dc.contributor.author |
Nielsen, Sebastian, R.
|
|
dc.contributor.author |
Hammer, Troels
|
|
dc.contributor.author |
Gibson, Josefine
|
|
dc.contributor.author |
Pepper, Michael Sean
|
|
dc.contributor.author |
Nisato, Riccardo E.
|
|
dc.contributor.author |
Dissing, Steen
|
|
dc.contributor.author |
Tritsaris, Katerina
|
|
dc.date.accessioned |
2016-11-04T05:11:57Z |
|
dc.date.available |
2016-11-04T05:11:57Z |
|
dc.date.issued |
2013-08 |
|
dc.description.abstract |
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, was 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. |
en_ZA |
dc.description.department |
Immunology |
en_ZA |
dc.description.librarian |
hb2016 |
en_ZA |
dc.description.sponsorship |
Grants from Center for
Healthy Ageing (Nordea Fonden), Novo Nordisk Fonden,
Carlsberg Fonden, Fonden til Lægevidenskabens Fremme
(AP Møller), Harboe Fonden, Psoriasis Fonden, and
Købmand M. Kristjan Kjær og Hustru Margrethe Kjær, Født
La Cour-Holmes Fond.
Remove selected |
en_ZA |
dc.description.uri |
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1549-8719 |
en_ZA |
dc.identifier.citation |
Nielsen, SR, Hammer, T, Gibson, J, Pepper, MS, Nisato, RE, Dissing, S & Tritsaris, K 2013, 'IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression', Microcirculation, vol. 20, no. 6, pp. 555-564. |
en_ZA |
dc.identifier.issn |
1073-9688 (print) |
|
dc.identifier.issn |
1549-8719 (online) |
|
dc.identifier.other |
10.1111/micc.12055 |
|
dc.identifier.uri |
http://hdl.handle.net/2263/57652 |
|
dc.language.iso |
en |
en_ZA |
dc.publisher |
Wiley |
en_ZA |
dc.rights |
© 2013 John Wiley & Sons Ltd. This is the pre-peer reviewed version of the following article : IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression, Microcirculation, vol. 20, no. 6, pp. 555-564, 2013. doi : 10.1111/micc.12055. The definite version is available at : http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1549-8719. |
en_ZA |
dc.subject |
IL-27 |
en_ZA |
dc.subject |
Lymphangiogenesis |
en_ZA |
dc.subject |
Proliferation |
en_ZA |
dc.subject |
STAT1 |
en_ZA |
dc.subject |
CXCL10 |
en_ZA |
dc.title |
IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression |
en_ZA |
dc.type |
Postprint Article |
en_ZA |