Interleukin-15 attenuates transforming growth factor-beta1-induced myofibroblast differentiation in human fetal lung fibroblasts.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1665075
- author
- Wuttge, Dirk LU ; Wildt, Marie LU ; Scheja, Agneta LU and Westergren-Thorsson, Gunilla LU
- organization
- publishing date
- 2010
- 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
- pmid:20732850
- 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
- 2016-04-04 08:25:40
- date last changed
- 2022-01-29 03:26:46
@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}},
doi = {{10.1684/ecn.2010.0202}},
volume = {{21}},
year = {{2010}},
}