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.
The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies / L., Di Luigi; M., Sottili; C., Antinozzi; G. B., Vannelli; Romanelli, Francesco; Riccieri, Valeria; Valesini, Guido; Lenzi, Andrea; C., Crescioli. - In: PLOS ONE. - ISSN 1932-6203. - STAMPA. - 8:10(2013), pp. 1-11. [10.1371/journal.pone.0077745]
The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies
ROMANELLI, Francesco;RICCIERI, Valeria;VALESINI, Guido;LENZI, Andrea;
2013
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.