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- Hesselstrand, Roger, et al.
(författare)
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Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis.
- 2013
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 107:7, s. 1079-1086
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Decision on treatment of systemic sclerosis (SSc) related interstitial lung disease (ILD) largely relies on the findings on high resolution computed tomography (HRCT) and there is a need for improvement in assessment of the fibrotic activity. The objectives of this study were to study biomarkers in bronchoalveolar lavage fluid (BALF) from SSc patients with ILD and to relate the findings to the severity and activity of lung fibrosis. METHODS: Fifteen patients with early SSc and 12 healthy controls were subjected to BAL. Cell counts and analyses of CXCL5, CXCL8 and S100A8/A9 were performed in BALF and serum. COMP and KL-6 were measured in serum. HRCT of lungs was quantified for ground glass opacities (GGO), reticulation and traction bronchiectases. RESULTS: BALF concentrations of CXCL8 (p < 0.001), CXCL5 (p = 0.002) and S100A8/A9 (p = 0.016) were higher in patients than controls. Serum KL-6 (p < 0.001) was increased in SSc patients and correlated with BALF concentration of eosinophils (rS = 0.57, p = 0.027). Patients with more widespread GGO on HRCT were characterised in BALF by a higher eosinophil count (p = 0.002) and in serum by higher KL-6 (p = 0.008). Patients with more fibrosis were characterised in BALF by higher eosinophil count (p = 0.014), higher CXCL8 (p = 0.005) and S100A8A/A9 (p = 0.014) concentration and in serum by a higher serum COMP (p = 0.023). CONCLUSIONS: In SSc related ILD, biomarkers from BALF and serum correlate to findings on HRCT suggesting usefulness as markers of presence and extent of lung fibrosis.
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| 2. |
- Wuttge, Dirk, et al.
(författare)
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Interleukin-15 attenuates transforming growth factor-beta1-induced myofibroblast differentiation in human fetal lung fibroblasts.
- 2010
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Ingår i: European Cytokine Network. - 1952-4005. ; 21, s. 165-176
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Tidskriftsartikel (refereegranskat)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.
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