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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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