Increased cysteinyl-leukotrienes and 8-isoprostane in exhaled breath condensate from systemic sclerosis patients

Tufvesson, Ellen; Božović, Gracijela; Hesselstrand, Roger; Bjermer, Leif; Scheja, Agneta; Wuttge, Dirk M.

doi:10.1093/rheumatology/keq271

Cited by 27 publications

(20 citation statements)

References 16 publications

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“…Although the concentration of LTB4 significantly correlated with the concentration of cysteinyl leukotrienes, the difference in LTB4 levels was not significant between SSc patients and the control group. No association was documented in this group between the leukotriene concentrations and radiological findings of HRCT or functional pulmonary tests [25]. There is no ready explanation for the discrepancies between measurements of www.fhc.viamedica.pl LTB4 in BALF and exhaled breath condensates; however, it could be due to the limited numbers of patients with SSc-ILD in the study by Tufvesson and/or the influence of treatment which could potentially alter leukotriene metabolism.…”

Section: Leukotrienes and Systemic Sclerosismentioning

confidence: 68%

“…Recently, Tufvesson et al measured the concentration of leukotrienes in exhaled breath condensates of 22 patients with SSc, including 12 patients with SSc-ILD as defined by the presence of traction bronchiectasis within areas of ground-glass opacities and/ /or reticulation in high resolution computed tomography (HRCT) of the lungs [25]. They showed that concentration of cysteinyl leukotrienes is significantly higher in exhaled breath condensates of SSc patients compared to healthy controls.…”

Section: Leukotrienes and Systemic Sclerosismentioning

confidence: 99%

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The role of leukotrienes in the pathogenesis of systemic sclerosis

Chwieśko-Minarowska

Kowal

Bielecki

et al. 2012

Folia Histochem Cytobiol.

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Systemic sclerosis (SSc, scleroderma) is an autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. SSc-related involvement of the lungs, heart, kidneys and/or the gastrointestinal system accounts for the increased mortality of scleroderma patients. Despite the progress which has recently been made in this field, the treatment of SSc is still unsatisfactory due to the low efficacy and/or high toxicity of available therapies. Leukotrienes are a family of lipid mediators synthesized from arachidonic acid in a process mediated by 5-lipoxygenase; they include leukotriene B4 and a group of cysteinyl leukotrienes: C4, D4, and E4. Leukotrienes play an important role in the regulation of all the processes vital to the pathogenesis of SSc, namely inflammation, vascular function and connective tissue remodeling. The available data suggests that an excessive synthesis of leukotrienes may contribute to the development and progression of SSc. Accordingly, blockade of leukotriene pathways appears to be a new, promising target for the treatment of

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Section: Leukotrienes and Systemic Sclerosismentioning

confidence: 68%

Section: Leukotrienes and Systemic Sclerosismentioning

confidence: 99%

The role of leukotrienes in the pathogenesis of systemic sclerosis

Chwieśko-Minarowska

Kowal

Bielecki

et al. 2012

Folia Histochem Cytobiol.

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“…There appear to be diseases where the 5-lipoxygenase pathway is constitutively activated and LTs are produced constantly, as in idiopathic pulmonary fibrosis 2) and systemic sclerosis 3) . LTs are involved in the pathogenesis of lung fibrosis by direct effects on migration, proliferation and matrix protein synthesis by fibroblasts, as well as by indirect effects, such as suppression of the production of antifibrogenic cytokines 4) .…”

Section: Introductionmentioning

confidence: 99%

Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

Pelclová¹,

Fenclová²,

Vlčková³

et al. 2012

Ind Health

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Leukotrienes (LTs) are involved in the pathogenesis of lung fibrosis and were increased in exhaled breath condensate (EBC) of the patients with pneumoconiosis. However the possible influence of extra-pulmonary disorders on the EBC markers is not known. Therefore in parallel with EBC, LTs' levels in the plasma and urine were measured in patients with pneumoconiosis (45 × asbestos exposure, 37 × silica exposure) and in 27 controls. Individual LTs B4, C4, D4 and E4 were measured by liquid chromatography − electrospray ionization − tandem mass spectrometry (LC-ESI-MS/MS). In EBC, LT D4 and LT E4 were increased in both groups of patients (p<0.001 and p<0.05), comparing with the controls. Both LT B4 and cysteinyl LTs were elevated in asbestosexposed subjects (p<0.05). Asbestosis with more severe radiological signs (s1/s2-t3/u2) and lung functions impairment has shown higher cysteinyl LTs and LT C4 in the EBC (p<0.05) than mild asbestosis (s1/s0-s1/s1). In addition, in the subjects with asbestosis, cysteinyl LTs in EBC correlated with TLC (−0.313, p<0.05) and TLCO/Hb (−0.307, p<0.05), and LT C4 with TLC (−0.358, p<0.05). In pneumoconioses, EBC appears the most useful from the 3 fluids studied.

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“…Additionally, increased urinary levels of 8-isoprostanes were previously found in SSc patients in the early stages of the disease (Cracowski et al, 2001). It has also been reported that 8-isoprostane in exhaled breath condensate of SSc patients is increased (Tufvesson et al, 2010). Similarly, it was demonstrated that bronchoalveolar lavage fuid from SSc patients with fibrosing alveolitis contained increased levels of 8-isoprostanes (Montuschi et al, 1998).…”

Section: Biomarkers Of Oxidative Stressmentioning

confidence: 93%

The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy

et al. 2018

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Systemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as ‘Raynaud’s phenomenon,’ which is often an indication of an underlying widespread vasculopathy. Although autoimmune responses and inflammation are both found to play an important role in the pathogenesis of this vasculopathy, no definite initiating factors have been identified. Recently, several studies have underlined the potential role of oxidative stress in the pathogenesis of SSc vasculopathy thereby proposing a new aspect in the pathogenesis of this disease. For instance, circulating levels of reactive oxygen species (ROS) related markers have been found to correlate with SSc vasculopathy, the formation of fibrosis and the production of autoantibodies. Excess ROS formation is well-known to lead to endothelial cell (EC) injury and vascular complications. Collectively, these findings suggest a potential role of ROS in the initiation and progression of SSc vasculopathy. In this review, we present the background of oxidative stress related processes (e.g., EC injury, autoimmunity, inflammation, and vascular wall remodeling) that may contribute to SSc vasculopathy. Finally, we describe the use of oxidative stress related read-outs as clinical biomarkers of disease activity and evaluate potential anti-oxidative strategies in SSc.

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Increased cysteinyl-leukotrienes and 8-isoprostane in exhaled breath condensate from systemic sclerosis patients

Cited by 27 publications

References 16 publications

The role of leukotrienes in the pathogenesis of systemic sclerosis

The role of leukotrienes in the pathogenesis of systemic sclerosis

Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy

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