@Article{ecn.2010.0202,
AUTHOR = {Dirk M. Wuttge, Marie Wildt, Agneta Scheja, Gunilla Westergren-Thorsson},
TITLE = {Interleukin-15 attenuates transforming growth factor-β1-induced myofibroblast differentiation in human fetal lung fibroblasts},
JOURNAL = {European Cytokine Network},
VOLUME = {21},
YEAR = {2010},
NUMBER = {3},
PAGES = {165--176},
URL = {http://www.techscience.com/ECN/v21n3/65854},
ISSN = {1952-4005},
ABSTRACT = {Objective. Fibroproliferative 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. Methods.
We used human fetal lung fibroblasts for the cytokine stimulation. As a marker of myofibroblast differentiation,
α-smooth muscle actin (α-SMA) was analyzed by western blot and quantitative real-time PCR. The well-known
profibrotic cytokine, transforming growth factor-β1(TGF-β1), was used for comparison, and TGF-β signaling
paths were also studied. Results. IL-15 did not induce α-SMA expression, a marker for myofibroblast differenti-ation.
Unexpectedly, IL-15 counteracted TGF-β1-mediated α-SMA expression. Moreover, TGF-β1-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-β signaling cascades. Conclusion. IL-15 has anti-fibrotic
properties that, speculatively however, may be insufficient in systemic sclerosis.},
DOI = {10.1684/ecn.2010.0202}
}