scholarly journals The Effect of Dexamethasone on Bleomycin-Induced Lung Fibrosis in the Mouse Model of Systemic Sclerosis

2018 ◽  
Vol 12 (8) ◽  
pp. 86-94
Author(s):  
Salar PashangZadeh ◽  
Marjan Taherian ◽  
Fatemeh Vafashoar ◽  
Ali Anisian ◽  
Kazem Mousavizadeh ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mouse Model ◽  
Lung Fibrosis

scholarly journals Progesterone Aggravates Lung Fibrosis in a Mouse Model of Systemic Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Fatemeh Vafashoar ◽  
Kazem Mousavizadeh ◽  
Hadi Poormoghim ◽  
Amir Haghighi ◽  
Salar Pashangzadeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Serum Level ◽  
Mouse Model ◽  
Autoimmune Diseases ◽  
Lung Fibrosis ◽  
Normal Lung ◽  
Related Factors ◽  
Progesterone Treatment ◽  
Injured Lung

BackgroundGender-related factors have explained the higher prevalence of autoimmune diseases in women. Sex hormones play a key role in the immune system and parenchymal cells function; therefore, these hormones can be important in the pathogenesis of autoimmune diseases as a risk or beneficial factor. Lung fibrosis is the main cause of mortality in systemic sclerosis, a female predominant autoimmune disease. The objective of this study was to examine the effect of progesterone on lung fibrosis in a mouse model of systemic sclerosis.MethodsMice with bleomycin-induced lung fibrosis treated with progesterone subcutaneously for 21 and 28 days. Blood was collected for hormone and cytokine measurement at the end of treatment then, skin and lung tissues were harvested for histological assessment, gene expression, cytokine, hydroxyproline, and gelatinase measurement.ResultsTrichrome staining and hydroxyproline measurements showed that progesterone treatment increased the content of collagen in fibrotic and normal lung tissues. Progesterone increased α-SMA (P < 0.01), TGF- β (P < 0.05) and decreased MMP9 (P < 0.05) in fibrotic lung tissues. Also progesterone treatment decreased the gene expression of Col1a2 (P <0.05), Ctgf (P <01), End1 (0.001) in bleomycin- injured lung tissues. The serum level of TNF-α was decreased, but the serum level of cortisol was increased by progesterone treatment in fibrotic mice (P< 0.05).ConclusionOur results showed that progesterone aggravates lung fibrosis in a mouse model of systemic sclerosis.

O04 In vivo assessment of prevention of lung fibrosis using the pan-PPAR agonist lanifibranor in the TbRIIDk-fib mouse model of systemic sclerosis

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_3) ◽  
Author(s):  
Emma Derrett-Smith ◽  
Xu Shi-Wen ◽  
David Abraham ◽  
Olivier Lacombe ◽  
Pierre Broqua ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mouse Model ◽  
Lung Fibrosis ◽  
Ppar Agonist ◽  
In Vivo Assessment

scholarly journals The pan-PPAR agonist lanifibranor reduces development of lung fibrosis and attenuates cardiorespiratory manifestations in a transgenic mouse model of systemic sclerosis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Emma Derrett-Smith ◽  
Kristina E. N. Clark ◽  
Xu Shiwen ◽  
David J. Abraham ◽  
Rachel K. Hoyles ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Mouse Model ◽  
Right Ventricular ◽  
Lung Fibrosis ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Ppar Agonist ◽  
The Impact ◽  
Ppar Pathway

Abstract Background The TβRII∆k-fib transgenic (TG) mouse model of scleroderma replicates key fibrotic and vasculopathic complications of systemic sclerosis through fibroblast-directed upregulation of TGFβ signalling. We have examined peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this model and explored the impact of the pan-PPAR agonist lanifibranor on the cardiorespiratory phenotype. Methods PPAR pathway gene and protein expression differences from TG and WT sex-matched littermate mice were determined at baseline and following administration of one of two doses of lanifibranor (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. The prevention of bleomycin-induced lung fibrosis and SU5416-induced pulmonary hypertension by lanifibranor was explored. Results Gene expression data were consistent with the downregulation of the PPAR pathway in the TβRII∆k-fib mouse model. TG mice treated with high-dose lanifibranor demonstrated significant protection from lung fibrosis after bleomycin and from right ventricular hypertrophy following induction of pulmonary hypertension by SU5416, despite no significant change in right ventricular systolic pressure. Conclusions In the TβRII∆k-fib mouse strain, treatment with 100 mg/kg lanifibranor reduces the development of lung fibrosis and right ventricular hypertrophy induced by bleomycin or SU5416, respectively. Reduced PPAR activity may contribute to the exaggerated fibroproliferative response to tissue injury in this transgenic model of scleroderma and its pulmonary complications.

scholarly journals Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity

2015 ◽  
Vol 57 (2) ◽  
pp. 133-141 ◽  
Author(s):  
Jing Chen ◽  
Yacheng Wang ◽  
Zijie Mei ◽  
Shimin Zhang ◽  
Jie Yang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lung Fibrosis ◽  
Tumor Bearing Mouse ◽  
Tumor Bearing ◽  
Type 2 Immunity ◽  
Radiation Induced

The involvement of leucine-rich α-2 glycoprotein in the progression of skin and lung fibrosis in bleomycin-induced systemic sclerosis model

2021 ◽  
pp. 1-10
Author(s):  
Hideki Nakajima ◽  
Kimiko Nakajima ◽  
Satoshi Serada ◽  
Minoru Fujimoto ◽  
Tetsuji Naka ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lung Fibrosis

Differences in Texture Analysis Parameters Between Active Alveolitis and Lung Fibrosis in Chest CT of Patients with Systemic Sclerosis

2017 ◽  
Vol 24 (12) ◽  
pp. 1596-1603 ◽  
Author(s):  
Christopher Kloth ◽  
Anya C. Blum ◽  
Wolfgang M. Thaiss ◽  
Heike Preibsch ◽  
Hendrik Ditt ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Texture Analysis ◽  
Lung Fibrosis ◽  
Chest Ct

scholarly journals IL-1 receptor blockade skews inflammation towards Th2 in a mouse model of systemic sclerosis

2019 ◽  
Vol 54 (3) ◽  
pp. 1900154 ◽  
Author(s):  
Anna Birnhuber ◽  
Slaven Crnkovic ◽  
Valentina Biasin ◽  
Leigh M. Marsh ◽  
Balazs Odler ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lung Function ◽  
Pulmonary Fibrosis ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Pulmonary Involvement ◽  
Specific Patient ◽  
Alternatively Activated Macrophages ◽  
Alternatively Activated

The interleukin (IL)-1 family of cytokines is strongly associated with systemic sclerosis (SSc) and pulmonary involvement, but the molecular mechanisms are poorly understood. The aim of this study was to assess the role of IL-1α and IL-1β in pulmonary vascular and interstitial remodelling in a mouse model of SSc.IL-1α and IL-1β were localised in lungs of SSc patients and in the fos-related antigen-2 (Fra-2) transgenic (TG) mouse model of SSc. Lung function, haemodynamic parameters and pulmonary inflammation were measured in Fra-2 TG mice with or without 8 weeks of treatment with the IL-1 receptor antagonist anakinra (25 mg·kg−1·day−1). Direct effects of IL-1 on pulmonary arterial smooth muscle cells (PASMCs) and parenchymal fibroblasts were investigated in vitro.Fra-2 TG mice exhibited increased collagen deposition in the lung, restrictive lung function and enhanced muscularisation of the vasculature with concomitant pulmonary hypertension reminiscent of the changes in SSc patients. Immunoreactivity of IL-1α and IL-1β was increased in Fra-2 TG mice and in patients with SSc. IL-1 stimulation reduced collagen expression in PASMCs and parenchymal fibroblasts via distinct signalling pathways. Blocking IL-1 signalling in Fra-2 TG worsened pulmonary fibrosis and restriction, enhanced T-helper cell type 2 (Th2) inflammation, and increased the number of pro-fibrotic, alternatively activated macrophages.Our data suggest that blocking IL-1 signalling as currently investigated in several clinical studies might aggravate pulmonary fibrosis in specific patient subsets due to Th2 skewing of immune responses and formation of alternatively activated pro-fibrogenic macrophages.

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