The Experts below are selected from a list of 36 Experts worldwide ranked by ideXlab platform
C Antinozzi - One of the best experts on this subject based on the ideXlab platform.
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Comparative study of testosterone and vitamin D analogue, Elocalcitol, on insulin-controlled signal transduction pathway regulation in human skeletal muscle cells
Journal of Endocrinological Investigation, 2019Co-Authors: C Antinozzi, Francesco Marampon, Paolo Sgro, Vincenzo Tombolini, Andrea Lenzi, Clara Crescioli, L Di LuigiAbstract:Purpose Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects. Aim To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and Elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets. Methods Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression. Results T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression. Conclusions All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.
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comparative study of testosterone and vitamin d analogue Elocalcitol on insulin controlled signal transduction pathway regulation in human skeletal muscle cells
Journal of Endocrinological Investigation, 2019Co-Authors: C Antinozzi, Francesco Marampon, Paolo Sgro, Vincenzo Tombolini, Andrea Lenzi, Clara Crescioli, L Di LuigiAbstract:Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects. To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and Elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets. Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression. T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression. All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.
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potential role for the vdr agonist Elocalcitol in metabolic control evidences in human skeletal muscle cells
The Journal of Steroid Biochemistry and Molecular Biology, 2017Co-Authors: C Antinozzi, Luigi Di Luigi, Clarissa Corinaldesi, Carla Giordano, Annalinda Pisano, Bruna Cerbelli, Silvia Migliaccio, Katia Stefanantoni, Gabriella B Vannelli, Salvatore MinisolaAbstract:Vitamin D plays a pivotal role to maintain skeletal muscle integrity and health. Vitamin D deficiency characterizes inflammatory myopathy (IM) and diabetes, often overlapping diseases involving skeletal muscle damage. Vitamin D receptor (VDR) agonists likely exert beneficial effects in both IM and metabolic disturbances. We aim to evaluate in vitro the effect of Elocalcitol, a non-hypercalcemic VDR agonist, on the biomolecular metabolic machinery of human skeletal muscle cells (Hfsmc), vs. insulin (I). We analyzed GLUT4, Flotillin-1, Caveolin-3 and Caveolin-1 cell expression/localization; mTOR, AKT, ERK and 4E-BP1 phosphorylation; IL-6 myokine release; VDR expression. We investigated in vivo vitamin D status in IM subjects, evaluating VDR muscular expression and serum vitamin D with metabolism-related parameters, as glycemia, triglycerides, cholesterol, resistin and adiponectin. In Hfsmc, Elocalcitol exerted an I-like effect, promoting GLUT4 re-localization in Flotillin-1, Caveolin-3 and Caveolin-1 positive sites and mTOR, AKT, ERK, 4E-BP1 activation; it enhanced IL-6 myokine release. IM subjects, all normoglycemic, showed VDR/vitamin D deficiency that, together with high lipidemic and resistin profile, possibly increases the risk to develop metabolic diseases. VDR agonists as Elocalcitol may be therapeutic tools for skeletal muscle integrity/function maintenance, an indispensable condition for health homeostasis.
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Effect of different immunosuppressors on cytokine-induced CXCL10 secretion in Hfsmc.
2013Co-Authors: Luigi Di Luigi, C Antinozzi, Andrea Lenzi, Mariangela Sottili, Gabriella Barbara Vannelli, Francesco Romanelli, Valeria Riccieri, Guido Valesini, Clara CrescioliAbstract:A, BXL-01-0029 (open triangles), Elocalcitol (closed triangles), MTX (open squares), CsA (closed circles) and MeP (open circles) dose-dependently inhibited IFNγ+TNFα-induced CXCL10 secretion (closed squares, taken as 100%, ) after 24 h. Simultaneous fitting of the curves showed that BXL-01-0029 and Elocalcitol retained the highest potency, as shown by the IC50s depicted in the inset of the figure. B, Neither infliximab (closed losangues, left) nor LEF (open losangues, right) exerted a dose-dependent inhibition of cytokine-induced CXCL10 secretion (closed squares, taken as 100%); IC50 s are reported in figure insets. C, At concentrations corresponding to the near therapy doses the inhibition by BXL-01-0029, not by Elocalcitol, was significantly higher than MeP-, CsA- and MTX-induced ones (*P
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The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies
'Public Library of Science (PLoS)', 2013Co-Authors: L Di Luigi, C Antinozzi, Andrea Lenzi, Francesco Romanelli, Valeria Riccieri, Guido Valesini, M. Sottili, G.b. Vannelli, Clara CrescioliAbstract:Objective:This study aims to investigatein vitro the effect of the VDR agonist BXL-01-0029 onto IFNc/TNFa-induced CXCL10 secretion by human skeletal muscle cells compared to Elocalcitol (VDR agonist), methylprednisolone, methotrexate, cyclosporin A, infliximab and leflunomide; to assessin vivo circulating CXCL10 level in subjects at time of diagnosis with IMs, before therapy, together with TNFa, IFNc, IL-8, IL-6, MCP-1, MIP-1band IL-10, vs. healthy subjects. Methods:Human fetal skeletal muscle cells were used forin vitro studies; ELISA and Bio-Plex were used to measure cell supernatant and IC50determination or serum cytokines; Western blot and Bio-Plex were for cell signaling analysis. Results:BXL-01-0029 decreased with the highest potency IFNc/TNFa-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFain human skeletal muscle cells; CXCL10 level was the highest in sera of subjects diagnosed with IMs before therapy and the only one significantly different vs. healthy controls. Conclusions:Ourin vitro andin vivo data, while confirm the relevance of CXCL10 in IMs, suggested BXL-01-0029 as a novel pharmacological tool for IM treatment, hypothetically to be used in combination with the current immunosuppressants to minimize side effects
Clara Crescioli - One of the best experts on this subject based on the ideXlab platform.
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Comparative study of testosterone and vitamin D analogue, Elocalcitol, on insulin-controlled signal transduction pathway regulation in human skeletal muscle cells
Journal of Endocrinological Investigation, 2019Co-Authors: C Antinozzi, Francesco Marampon, Paolo Sgro, Vincenzo Tombolini, Andrea Lenzi, Clara Crescioli, L Di LuigiAbstract:Purpose Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects. Aim To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and Elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets. Methods Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression. Results T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression. Conclusions All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.
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comparative study of testosterone and vitamin d analogue Elocalcitol on insulin controlled signal transduction pathway regulation in human skeletal muscle cells
Journal of Endocrinological Investigation, 2019Co-Authors: C Antinozzi, Francesco Marampon, Paolo Sgro, Vincenzo Tombolini, Andrea Lenzi, Clara Crescioli, L Di LuigiAbstract:Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects. To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and Elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets. Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression. T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression. All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.
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Effect of different immunosuppressors on cytokine-induced CXCL10 secretion in Hfsmc.
2013Co-Authors: Luigi Di Luigi, C Antinozzi, Andrea Lenzi, Mariangela Sottili, Gabriella Barbara Vannelli, Francesco Romanelli, Valeria Riccieri, Guido Valesini, Clara CrescioliAbstract:A, BXL-01-0029 (open triangles), Elocalcitol (closed triangles), MTX (open squares), CsA (closed circles) and MeP (open circles) dose-dependently inhibited IFNγ+TNFα-induced CXCL10 secretion (closed squares, taken as 100%, ) after 24 h. Simultaneous fitting of the curves showed that BXL-01-0029 and Elocalcitol retained the highest potency, as shown by the IC50s depicted in the inset of the figure. B, Neither infliximab (closed losangues, left) nor LEF (open losangues, right) exerted a dose-dependent inhibition of cytokine-induced CXCL10 secretion (closed squares, taken as 100%); IC50 s are reported in figure insets. C, At concentrations corresponding to the near therapy doses the inhibition by BXL-01-0029, not by Elocalcitol, was significantly higher than MeP-, CsA- and MTX-induced ones (*P
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The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies
'Public Library of Science (PLoS)', 2013Co-Authors: L Di Luigi, C Antinozzi, Andrea Lenzi, Francesco Romanelli, Valeria Riccieri, Guido Valesini, M. Sottili, G.b. Vannelli, Clara CrescioliAbstract:Objective:This study aims to investigatein vitro the effect of the VDR agonist BXL-01-0029 onto IFNc/TNFa-induced CXCL10 secretion by human skeletal muscle cells compared to Elocalcitol (VDR agonist), methylprednisolone, methotrexate, cyclosporin A, infliximab and leflunomide; to assessin vivo circulating CXCL10 level in subjects at time of diagnosis with IMs, before therapy, together with TNFa, IFNc, IL-8, IL-6, MCP-1, MIP-1band IL-10, vs. healthy subjects. Methods:Human fetal skeletal muscle cells were used forin vitro studies; ELISA and Bio-Plex were used to measure cell supernatant and IC50determination or serum cytokines; Western blot and Bio-Plex were for cell signaling analysis. Results:BXL-01-0029 decreased with the highest potency IFNc/TNFa-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFain human skeletal muscle cells; CXCL10 level was the highest in sera of subjects diagnosed with IMs before therapy and the only one significantly different vs. healthy controls. Conclusions:Ourin vitro andin vivo data, while confirm the relevance of CXCL10 in IMs, suggested BXL-01-0029 as a novel pharmacological tool for IM treatment, hypothetically to be used in combination with the current immunosuppressants to minimize side effects
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The Vitamin D Receptor Agonist BXL-01-0029 as a Potential New Pharmacological Tool for the Treatment of Inflammatory Myopathies
2013Co-Authors: Luigi Di Luigi, C Antinozzi, Andrea Lenzi, Mariangela Sottili, Gabriella Barbara Vannelli, Francesco Romanelli, Valeria Riccieri, Guido Valesini, Clara CrescioliAbstract:Objective: This study aims to investigate in vitro the effect of the VDR agonist BXL-01-0029 onto IFNc/TNFa-induced CXCL10 secretion by human skeletal muscle cells compared to Elocalcitol (VDR agonist), methylprednisolone, methotrexate, cyclosporin A, infliximab and leflunomide; to assess in vivo circulating CXCL10 level in subjects at time of diagnosis with IMs, before therapy, together with TNFa, IFNc, IL-8, IL-6, MCP-1, MIP-1b and IL-10, vs. healthy subjects. Methods: Human fetal skeletal muscle cells were used for in vitro studies; ELISA and Bio-Plex were used to measure cell supernatant and IC50 determination or serum cytokines; Western blot and Bio-Plex were for cell signaling analysis. Results: BXL-01-0029 decreased with the highest potency IFNc/TNFa-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFa in human skeletal muscle cells; CXCL10 level was the highest in sera of subjects diagnosed with IMs before therapy and the only one significantly different vs. healthy controls. Conclusions: Our in vitro and in vivo data, while confirm the relevance of CXCL10 in IMs, suggested BXL-01-0029 as a novel pharmacological tool for IM treatment, hypothetically to be used in combination with the current immunosuppressants t
L Di Luigi - One of the best experts on this subject based on the ideXlab platform.
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Comparative study of testosterone and vitamin D analogue, Elocalcitol, on insulin-controlled signal transduction pathway regulation in human skeletal muscle cells
Journal of Endocrinological Investigation, 2019Co-Authors: C Antinozzi, Francesco Marampon, Paolo Sgro, Vincenzo Tombolini, Andrea Lenzi, Clara Crescioli, L Di LuigiAbstract:Purpose Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects. Aim To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and Elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets. Methods Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression. Results T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression. Conclusions All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.
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comparative study of testosterone and vitamin d analogue Elocalcitol on insulin controlled signal transduction pathway regulation in human skeletal muscle cells
Journal of Endocrinological Investigation, 2019Co-Authors: C Antinozzi, Francesco Marampon, Paolo Sgro, Vincenzo Tombolini, Andrea Lenzi, Clara Crescioli, L Di LuigiAbstract:Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects. To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and Elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets. Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression. T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression. All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.
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The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies
'Public Library of Science (PLoS)', 2013Co-Authors: L Di Luigi, C Antinozzi, Andrea Lenzi, Francesco Romanelli, Valeria Riccieri, Guido Valesini, M. Sottili, G.b. Vannelli, Clara CrescioliAbstract:Objective:This study aims to investigatein vitro the effect of the VDR agonist BXL-01-0029 onto IFNc/TNFa-induced CXCL10 secretion by human skeletal muscle cells compared to Elocalcitol (VDR agonist), methylprednisolone, methotrexate, cyclosporin A, infliximab and leflunomide; to assessin vivo circulating CXCL10 level in subjects at time of diagnosis with IMs, before therapy, together with TNFa, IFNc, IL-8, IL-6, MCP-1, MIP-1band IL-10, vs. healthy subjects. Methods:Human fetal skeletal muscle cells were used forin vitro studies; ELISA and Bio-Plex were used to measure cell supernatant and IC50determination or serum cytokines; Western blot and Bio-Plex were for cell signaling analysis. Results:BXL-01-0029 decreased with the highest potency IFNc/TNFa-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFain human skeletal muscle cells; CXCL10 level was the highest in sera of subjects diagnosed with IMs before therapy and the only one significantly different vs. healthy controls. Conclusions:Ourin vitro andin vivo data, while confirm the relevance of CXCL10 in IMs, suggested BXL-01-0029 as a novel pharmacological tool for IM treatment, hypothetically to be used in combination with the current immunosuppressants to minimize side effects
Andrea Lenzi - One of the best experts on this subject based on the ideXlab platform.
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Comparative study of testosterone and vitamin D analogue, Elocalcitol, on insulin-controlled signal transduction pathway regulation in human skeletal muscle cells
Journal of Endocrinological Investigation, 2019Co-Authors: C Antinozzi, Francesco Marampon, Paolo Sgro, Vincenzo Tombolini, Andrea Lenzi, Clara Crescioli, L Di LuigiAbstract:Purpose Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects. Aim To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and Elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets. Methods Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression. Results T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression. Conclusions All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.
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comparative study of testosterone and vitamin d analogue Elocalcitol on insulin controlled signal transduction pathway regulation in human skeletal muscle cells
Journal of Endocrinological Investigation, 2019Co-Authors: C Antinozzi, Francesco Marampon, Paolo Sgro, Vincenzo Tombolini, Andrea Lenzi, Clara Crescioli, L Di LuigiAbstract:Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects. To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and Elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets. Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression. T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression. All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.
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Effect of different immunosuppressors on cytokine-induced CXCL10 secretion in Hfsmc.
2013Co-Authors: Luigi Di Luigi, C Antinozzi, Andrea Lenzi, Mariangela Sottili, Gabriella Barbara Vannelli, Francesco Romanelli, Valeria Riccieri, Guido Valesini, Clara CrescioliAbstract:A, BXL-01-0029 (open triangles), Elocalcitol (closed triangles), MTX (open squares), CsA (closed circles) and MeP (open circles) dose-dependently inhibited IFNγ+TNFα-induced CXCL10 secretion (closed squares, taken as 100%, ) after 24 h. Simultaneous fitting of the curves showed that BXL-01-0029 and Elocalcitol retained the highest potency, as shown by the IC50s depicted in the inset of the figure. B, Neither infliximab (closed losangues, left) nor LEF (open losangues, right) exerted a dose-dependent inhibition of cytokine-induced CXCL10 secretion (closed squares, taken as 100%); IC50 s are reported in figure insets. C, At concentrations corresponding to the near therapy doses the inhibition by BXL-01-0029, not by Elocalcitol, was significantly higher than MeP-, CsA- and MTX-induced ones (*P
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The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies
'Public Library of Science (PLoS)', 2013Co-Authors: L Di Luigi, C Antinozzi, Andrea Lenzi, Francesco Romanelli, Valeria Riccieri, Guido Valesini, M. Sottili, G.b. Vannelli, Clara CrescioliAbstract:Objective:This study aims to investigatein vitro the effect of the VDR agonist BXL-01-0029 onto IFNc/TNFa-induced CXCL10 secretion by human skeletal muscle cells compared to Elocalcitol (VDR agonist), methylprednisolone, methotrexate, cyclosporin A, infliximab and leflunomide; to assessin vivo circulating CXCL10 level in subjects at time of diagnosis with IMs, before therapy, together with TNFa, IFNc, IL-8, IL-6, MCP-1, MIP-1band IL-10, vs. healthy subjects. Methods:Human fetal skeletal muscle cells were used forin vitro studies; ELISA and Bio-Plex were used to measure cell supernatant and IC50determination or serum cytokines; Western blot and Bio-Plex were for cell signaling analysis. Results:BXL-01-0029 decreased with the highest potency IFNc/TNFa-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFain human skeletal muscle cells; CXCL10 level was the highest in sera of subjects diagnosed with IMs before therapy and the only one significantly different vs. healthy controls. Conclusions:Ourin vitro andin vivo data, while confirm the relevance of CXCL10 in IMs, suggested BXL-01-0029 as a novel pharmacological tool for IM treatment, hypothetically to be used in combination with the current immunosuppressants to minimize side effects
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The Vitamin D Receptor Agonist BXL-01-0029 as a Potential New Pharmacological Tool for the Treatment of Inflammatory Myopathies
2013Co-Authors: Luigi Di Luigi, C Antinozzi, Andrea Lenzi, Mariangela Sottili, Gabriella Barbara Vannelli, Francesco Romanelli, Valeria Riccieri, Guido Valesini, Clara CrescioliAbstract:Objective: This study aims to investigate in vitro the effect of the VDR agonist BXL-01-0029 onto IFNc/TNFa-induced CXCL10 secretion by human skeletal muscle cells compared to Elocalcitol (VDR agonist), methylprednisolone, methotrexate, cyclosporin A, infliximab and leflunomide; to assess in vivo circulating CXCL10 level in subjects at time of diagnosis with IMs, before therapy, together with TNFa, IFNc, IL-8, IL-6, MCP-1, MIP-1b and IL-10, vs. healthy subjects. Methods: Human fetal skeletal muscle cells were used for in vitro studies; ELISA and Bio-Plex were used to measure cell supernatant and IC50 determination or serum cytokines; Western blot and Bio-Plex were for cell signaling analysis. Results: BXL-01-0029 decreased with the highest potency IFNc/TNFa-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFa in human skeletal muscle cells; CXCL10 level was the highest in sera of subjects diagnosed with IMs before therapy and the only one significantly different vs. healthy controls. Conclusions: Our in vitro and in vivo data, while confirm the relevance of CXCL10 in IMs, suggested BXL-01-0029 as a novel pharmacological tool for IM treatment, hypothetically to be used in combination with the current immunosuppressants t
Luigi Di Luigi - One of the best experts on this subject based on the ideXlab platform.
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potential role for the vdr agonist Elocalcitol in metabolic control evidences in human skeletal muscle cells
The Journal of Steroid Biochemistry and Molecular Biology, 2017Co-Authors: C Antinozzi, Luigi Di Luigi, Clarissa Corinaldesi, Carla Giordano, Annalinda Pisano, Bruna Cerbelli, Silvia Migliaccio, Katia Stefanantoni, Gabriella B Vannelli, Salvatore MinisolaAbstract:Vitamin D plays a pivotal role to maintain skeletal muscle integrity and health. Vitamin D deficiency characterizes inflammatory myopathy (IM) and diabetes, often overlapping diseases involving skeletal muscle damage. Vitamin D receptor (VDR) agonists likely exert beneficial effects in both IM and metabolic disturbances. We aim to evaluate in vitro the effect of Elocalcitol, a non-hypercalcemic VDR agonist, on the biomolecular metabolic machinery of human skeletal muscle cells (Hfsmc), vs. insulin (I). We analyzed GLUT4, Flotillin-1, Caveolin-3 and Caveolin-1 cell expression/localization; mTOR, AKT, ERK and 4E-BP1 phosphorylation; IL-6 myokine release; VDR expression. We investigated in vivo vitamin D status in IM subjects, evaluating VDR muscular expression and serum vitamin D with metabolism-related parameters, as glycemia, triglycerides, cholesterol, resistin and adiponectin. In Hfsmc, Elocalcitol exerted an I-like effect, promoting GLUT4 re-localization in Flotillin-1, Caveolin-3 and Caveolin-1 positive sites and mTOR, AKT, ERK, 4E-BP1 activation; it enhanced IL-6 myokine release. IM subjects, all normoglycemic, showed VDR/vitamin D deficiency that, together with high lipidemic and resistin profile, possibly increases the risk to develop metabolic diseases. VDR agonists as Elocalcitol may be therapeutic tools for skeletal muscle integrity/function maintenance, an indispensable condition for health homeostasis.
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Effect of different immunosuppressors on cytokine-induced CXCL10 secretion in Hfsmc.
2013Co-Authors: Luigi Di Luigi, C Antinozzi, Andrea Lenzi, Mariangela Sottili, Gabriella Barbara Vannelli, Francesco Romanelli, Valeria Riccieri, Guido Valesini, Clara CrescioliAbstract:A, BXL-01-0029 (open triangles), Elocalcitol (closed triangles), MTX (open squares), CsA (closed circles) and MeP (open circles) dose-dependently inhibited IFNγ+TNFα-induced CXCL10 secretion (closed squares, taken as 100%, ) after 24 h. Simultaneous fitting of the curves showed that BXL-01-0029 and Elocalcitol retained the highest potency, as shown by the IC50s depicted in the inset of the figure. B, Neither infliximab (closed losangues, left) nor LEF (open losangues, right) exerted a dose-dependent inhibition of cytokine-induced CXCL10 secretion (closed squares, taken as 100%); IC50 s are reported in figure insets. C, At concentrations corresponding to the near therapy doses the inhibition by BXL-01-0029, not by Elocalcitol, was significantly higher than MeP-, CsA- and MTX-induced ones (*P
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The Vitamin D Receptor Agonist BXL-01-0029 as a Potential New Pharmacological Tool for the Treatment of Inflammatory Myopathies
2013Co-Authors: Luigi Di Luigi, C Antinozzi, Andrea Lenzi, Mariangela Sottili, Gabriella Barbara Vannelli, Francesco Romanelli, Valeria Riccieri, Guido Valesini, Clara CrescioliAbstract:Objective: This study aims to investigate in vitro the effect of the VDR agonist BXL-01-0029 onto IFNc/TNFa-induced CXCL10 secretion by human skeletal muscle cells compared to Elocalcitol (VDR agonist), methylprednisolone, methotrexate, cyclosporin A, infliximab and leflunomide; to assess in vivo circulating CXCL10 level in subjects at time of diagnosis with IMs, before therapy, together with TNFa, IFNc, IL-8, IL-6, MCP-1, MIP-1b and IL-10, vs. healthy subjects. Methods: Human fetal skeletal muscle cells were used for in vitro studies; ELISA and Bio-Plex were used to measure cell supernatant and IC50 determination or serum cytokines; Western blot and Bio-Plex were for cell signaling analysis. Results: BXL-01-0029 decreased with the highest potency IFNc/TNFa-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFa in human skeletal muscle cells; CXCL10 level was the highest in sera of subjects diagnosed with IMs before therapy and the only one significantly different vs. healthy controls. Conclusions: Our in vitro and in vivo data, while confirm the relevance of CXCL10 in IMs, suggested BXL-01-0029 as a novel pharmacological tool for IM treatment, hypothetically to be used in combination with the current immunosuppressants t