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

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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. 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. IL-15 did not induce α-SMA expression, a marker for myofibroblast differentiation. 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. IL-15 has anti-fibrotic properties that, speculatively however, may be insufficient in systemic sclerosis.