OBJECTIVE: This study aims to investigate in vitro the effect of the VDR agonist BXL-01-0029 onto IFNγ/TNFα-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 TNFα, IFNγ, IL-8, IL-6, MCP-1, MIP-1β 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 IFNγ/TNFα-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFα 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 to minimize side effects.

The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies / Di Luigi L; Sottili M; Antinozzi C; Vannelli GB; Romanelli F; Riccieri V; Valesini G; Lenzi A; Crescioli C.. - In: PLOS ONE. - ISSN 1932-6203. - STAMPA. - 8:(2013), pp. e77745-e77756.

The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies.

SOTTILI, MARIANGELA;VANNELLI, GABRIELLA;
2013

Abstract

OBJECTIVE: This study aims to investigate in vitro the effect of the VDR agonist BXL-01-0029 onto IFNγ/TNFα-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 TNFα, IFNγ, IL-8, IL-6, MCP-1, MIP-1β 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 IFNγ/TNFα-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFα 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 to minimize side effects.
2013
8
e77745
e77756
Di Luigi L; Sottili M; Antinozzi C; Vannelli GB; Romanelli F; Riccieri V; Valesini G; Lenzi A; Crescioli C.
File in questo prodotto:
File Dimensione Formato  
journal.pone.0077745.PDF

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Creative commons
Dimensione 1.14 MB
Formato Adobe PDF
1.14 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/958564
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 23
  • ???jsp.display-item.citation.isi??? 21
social impact