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Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Key points: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM).In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6‐month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics.We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls.A 6‐month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids.These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms. Exercise improves skeletal muscle function, clinical state and quality of life in patients with idiopathic inflammatory myopathy (IIM). Our aim was to identify disease‐related metabolic perturbations and the impact of exercise in skeletal muscle cells of IIM patients. Patients underwent a 6‐month intensive supervised training intervention. Muscle function, anthropometric and metabolic parameters were examined and muscle cell cultures were established (m. vastus lateralis; Bergström needle biopsy) before and after training from patients and sedentary age/sex/body mass index‐matched controls. [14C]Palmitate was used to determine fat oxidation and lipid synthesis (thin layer chromatography). Cells were exposed to a chronic (3 days) and acute (3 h) metabolic challenge (the saturated fatty acid palmitate, 100 μm). Reduced oxidative (intermediate metabolites, −49%, P = 0.034) and non‐oxidative (diglycerides, −38%, P = 0.013) lipid metabolism was identified in palmitate‐treated muscle cells from IIM patients compared to controls. Three days of palmitate exposure elicited distinct regulation of oxidative phosphorylation (OxPHOS) complex IV and complex V/ATP synthase (P = 0.012/0.005) and adipose triglyceride lipase in patients compared to controls (P = 0.045) (immunoblotting). Importantly, 6 months of training in IIM patients improved lipid metabolism (CO2, P = 0.010; intermediate metabolites, P = 0.041) and activation of AMP kinase (P = 0.007), and nearly normalized palmitate‐induced changes in OxPHOS proteins in myotubes from IIM patients, in parallel with improvements of patients' clinical state. Myotubes from IIM patients displayed altered dynamics of lipid metabolism and impaired response to metabolic challenge with saturated fatty acid. Our observations suggest that metabolic defects intrinsic to skeletal muscle could represent non‐immune pathomechanisms, which can contribute to muscle weakness in IIM. A 6‐month training intervention mitigated disease effects in muscle cells in vitro, indicating the existence of epigenetic regulatory mechanisms. Key points: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM).In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6‐month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics.We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls.A 6‐month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids.These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms. [ABSTRACT FROM AUTHOR]

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Systemic sclerosis (SSc) is a rare, chronic connective tissue disease affecting the skin, vessels, musculoskeletal system and internal organs. Despite advances in pharmacotherapy of organ manifestation and new knowledge about the pathogenesis of SSc, there is still no effective treatment of this serious disease. The aim of this review is to introduce traditional, most commonly used experimental animal models of SSc, clarify their basic pathomechanism, describe the advantages and limitations and outline their use in preclinical tests of potential therapeutic agents with subsequent clinical trials in patients with SSc. [ABSTRACT FROM AUTHOR]

Introduction: Systemic sclerosis (SSc) is a generalized connective tissue disease affecting the skin and internal organs. The pathogenesis of SSc is characterized by inflammation, vasculopathy and fibrosis. To date, none of the tested drugs have demonstrated convincing efficacy in the treatment of SSc. S100A4 is involved in the regulation of cell motility, proliferation, apoptosis, angiogenesis and remodeling of the extracellular matrix. It was originally described as a promoter of metastasis in tumors, however, its pro-inflammatory properties have recently been demonstrated in inflammatory rheumatic diseases. The aim of this study was to assess the role of S100A4 in pathological activation of fibroblasts in SSc and in experimental models of dermal fibrosis. Results: The expression of S100A4 was increased in the skin of SSc patients, in SSc fibroblasts and in experimental fibrosis in a TGF-β / Smad dependent manner. Overexpression of S100A4 or stimulation with recombinant S100A4 induced an activated phenotype in resting normal fibroblasts. In contrast, inhibition of S100A4 or its complete deficit abrogated the pro- -fibrotic effects of TGF-β and decreased the release of collagen. S100A4 knock-out mice (S100A4-/-) were reduced dermal thickening, decreased hydroxyproline content and lower counts of activated fibroblasts, so called myofibroblasts. Similarly, deficiency of S100A4 also ameliorated fibrosis in the Tight skin-1 (Tsk-1) mouse model. Anti-fibrotic effects of the inactivation of S100A4 in both experimental models of dermal fibrosis were mediated by inhibition of TGF-β / Smad signaling. Conclusion: Our results characterize S100A4 as a positive regulator of the stimmulatory effects of TGF-β on fibroblasts in SSc. S100A4 is induced by TGF-β and in turn amplifies the stimulatory effects of canonical TGF-β / Smad signaling on collagen synthesis by SSc fibroblasts and on induction of fibrosis. Since S100A4 is essentially required for the pro-fibrotic effects of TGF-β and neutralizing antibodies against S100A4 are currently evaluated in tumors, S100A4 might become a candidate molecule for novel anti-fibrotic therapies. [ABSTRACT FROM AUTHOR]