title: APL-1, an altered peptide ligand derived from heat-shock protein, alone or combined with methotrexate attenuates murine collagen-induced arthritis.
abstract: Induction of tolerance to autoantigens in vivo is a complex process that involves several mechanisms such as the induction of regulatory T cells and changes in the cytokine and chemokine profiles. This approach represents an attractive alternative for treatment of autoimmune diseases. APL-1 is an altered peptide ligand derived from a novel CD4 + T cell epitope of human heat-shock protein of 60 kDa (HSP60), an autoantigen involved in the pathogenesis of rheumatoid arthritis (RA). We have shown previously that this peptide efficiently inhibited the course of adjuvant-induced arthritis in Lewis rats and induced regulatory T cell (Treg) in ex vivo assay with PBMC isolated from RA patients. This study was undertaken to evaluate the therapeutic effect of APL-1 and its combination with methotrexate (MTX) in collagen-induced arthritis (CIA). CIA was induced in male DBA/1 mice at 8 weeks of age by immunization with chicken collagen. APL, MTX or both were administrated beginning from arthritis onset. Therapeutic effect was evaluated by arthritis and joint pathologic scores. In addition, TNFα and IL-10 in sera were measured by ELISA. Treg induction was assessed by FACS analysis. APL-1 inhibits efficiently the course of arthritis in CIA, similar to MTX. In addition, therapy with APL-1 plus MTX reduced CIA in mice, associated with an increase in Treg. These facts reinforce the therapeutic possibilities of APL-1 as a candidate drug for treatment of RA.
authors.affiliation: Biomedical Research Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, 10600, Havana, Cuba.
authors.forename: Norailys
authors.initials: N
authors.lastname: Lorenzo
authors.affiliation: Department of Genetics, Biology and Biochemistry, Molecular Biotechnology Center, Turin, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.affiliation: Department of Genetics, Biology and Biochemistry, Molecular Biotechnology Center, Turin, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Silengo
authors.affiliation: Biomedical Research Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, 10600, Havana, Cuba. mcarmen.dominguez@cigb.edu.cu.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Carmen Dominguez
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008811:Mice, Inbred DBA; D010455:Peptides / Q000008:administration & dosage*; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D006360:Heat-Shock Proteins; D007155:Immunologic Factors; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008727:Methotrexate
keywords: APL; Collagen-induced arthritis; HSP60; Rheumatoid arthritis; Treg