title: The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies.
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.
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Luigi
authors.forename: Mariangela
authors.initials: M
authors.lastname: Sottili
authors.forename: Cristina
authors.initials: C
authors.lastname: Antinozzi
authors.forename: Gabriella Barbara
authors.initials: GB
authors.lastname: Vannelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Romanelli
authors.forename: Valeria
authors.initials: V
authors.lastname: Riccieri
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.forename: Clara
authors.initials: C
authors.lastname: Crescioli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009220:Myositis / Q000188:drug therapy* / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D007166:Immunosuppressive Agents; D007378:Interleukins; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma