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Interleukin-15 attenuates transforming growth factor-beta1-induced myofibroblast differentiation in human fetal lung fibroblasts.

Wuttge, Dirk LU ; Wildt, Marie LU ; Scheja, Agneta LU and Westergren-Thorsson, Gunilla LU (2010) In European Cytokine Network 21. p.165-176
Abstract
ObjectiveFibroproliferative diseases are common causes of morbidity and mortality. Interleukin-15 (IL-15) is a pleiotropic cytokine with multiple effects on cells of the immune system. Although IL-15 is also expressed in mesenchymal cells, its effects on the development of fibrosis are unknown. We have previously described an association between serum IL-15 levels and the extent of pulmonary fibrosis in the connective tissue disease systemic sclerosis, suggesting that IL-15 may have profibrotic effects. To test this hypothesis, we studied the effects of IL-15 on myofibroblast differentiation, an in vitro model of fibrosis development.MethodsWe used human fetal lung fibroblasts for the cytokine stimulation. As a marker of myofibroblast... (More)
ObjectiveFibroproliferative diseases are common causes of morbidity and mortality. Interleukin-15 (IL-15) is a pleiotropic cytokine with multiple effects on cells of the immune system. Although IL-15 is also expressed in mesenchymal cells, its effects on the development of fibrosis are unknown. We have previously described an association between serum IL-15 levels and the extent of pulmonary fibrosis in the connective tissue disease systemic sclerosis, suggesting that IL-15 may have profibrotic effects. To test this hypothesis, we studied the effects of IL-15 on myofibroblast differentiation, an in vitro model of fibrosis development.MethodsWe used human fetal lung fibroblasts for the cytokine stimulation. As a marker of myofibroblast differentiation, alpha-smooth muscle actin (alpha-SMA) was analyzed by western blot and quantitative real-time PCR. The well-known profibrotic cytokine, transforming growth factor-beta1(TGF-beta1), was used for comparison, and TGF-beta signaling paths were also studied.ResultsIL-15 did not induce alpha-SMA expression, a marker for myofibroblast differentiation. Unexpectedly, IL-15 counteracted TGF-beta1-mediated alpha-SMA expression. Moreover, TGF-beta1-induced expression of collagen, fibronectin and connective tissue growth factor was attenuated by addition of IL-15. There was no effect of IL-15 on early events in the TGF-beta signaling cascades.ConclusionIL-15 has anti-fibrotic properties that, speculatively however, may be insufficient in systemic sclerosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Cytokine Network
volume
21
pages
165 - 176
publisher
John Libbey Eurotext
external identifiers
  • wos:000281962000003
  • pmid:20732850
  • scopus:77957377831
ISSN
1952-4005
DOI
10.1684/ecn.2010.0202
language
English
LU publication?
yes
id
825b8770-fbd8-43f7-b823-6538ed7c29d2 (old id 1665075)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20732850?dopt=Abstract
date added to LUP
2010-09-03 11:13:38
date last changed
2018-05-29 11:34:32
@article{825b8770-fbd8-43f7-b823-6538ed7c29d2,
  abstract     = {ObjectiveFibroproliferative diseases are common causes of morbidity and mortality. Interleukin-15 (IL-15) is a pleiotropic cytokine with multiple effects on cells of the immune system. Although IL-15 is also expressed in mesenchymal cells, its effects on the development of fibrosis are unknown. We have previously described an association between serum IL-15 levels and the extent of pulmonary fibrosis in the connective tissue disease systemic sclerosis, suggesting that IL-15 may have profibrotic effects. To test this hypothesis, we studied the effects of IL-15 on myofibroblast differentiation, an in vitro model of fibrosis development.MethodsWe used human fetal lung fibroblasts for the cytokine stimulation. As a marker of myofibroblast differentiation, alpha-smooth muscle actin (alpha-SMA) was analyzed by western blot and quantitative real-time PCR. The well-known profibrotic cytokine, transforming growth factor-beta1(TGF-beta1), was used for comparison, and TGF-beta signaling paths were also studied.ResultsIL-15 did not induce alpha-SMA expression, a marker for myofibroblast differentiation. Unexpectedly, IL-15 counteracted TGF-beta1-mediated alpha-SMA expression. Moreover, TGF-beta1-induced expression of collagen, fibronectin and connective tissue growth factor was attenuated by addition of IL-15. There was no effect of IL-15 on early events in the TGF-beta signaling cascades.ConclusionIL-15 has anti-fibrotic properties that, speculatively however, may be insufficient in systemic sclerosis.},
  author       = {Wuttge, Dirk and Wildt, Marie and Scheja, Agneta and Westergren-Thorsson, Gunilla},
  issn         = {1952-4005},
  language     = {eng},
  pages        = {165--176},
  publisher    = {John Libbey Eurotext},
  series       = {European Cytokine Network},
  title        = {Interleukin-15 attenuates transforming growth factor-beta1-induced myofibroblast differentiation in human fetal lung fibroblasts.},
  url          = {http://dx.doi.org/10.1684/ecn.2010.0202},
  volume       = {21},
  year         = {2010},
}