Therapeutic effect of an altered peptide ligand derived from heat-shock protein 60 by suppressing of inflammatory cytokines secretion in two animal models of rheumatoid arthritis

Autor:	Noraylis Lorenzo, F Altruda, O Reyes, J Ancizar, Isabel M. Hernandez, Rafael Gil, Gabriel Padrón, Ana María Torres, Maria Victoria Hernández, Ariana Barberá, L Silengo, Maria del Carmen Dominguez, H Garay
Rok vydání:	2012
Předmět:	T-Lymphocytes medicine.medical_treatment T cell Molecular Sequence Data Immunology Epitopes T-Lymphocyte Arthritis Inflammation Ligands Lymphocyte Activation Epitope Cell cycle phase Proinflammatory cytokine Arthritis Rheumatoid Mice medicine Animals Humans Immunology and Allergy Amino Acid Sequence business.industry Interleukin-17 T-cell receptor Chaperonin 60 medicine.disease Rats Disease Models Animal Treatment Outcome Cytokine medicine.anatomical_structure Amino Acid Substitution Mice Inbred DBA Rats Inbred Lew Cytokines Female medicine.symptom Peptides business
Zdroj:	Autoimmunity. 45:449-459
ISSN:	1607-842X 0891-6934
DOI:	10.3109/08916934.2012.697592
Popis:	Rheumatoid arthritis is a systemic autoimmune disease mediated by T cells. Productive engagement of T cell receptors by major histocompatibility complex-peptide leads to proliferation, differentiation and the definition of effector functions. Altered peptide ligands (APL) generated by amino acid substitutions in the antigenic peptide have diverse effects on T cell response. We predicted a novel T cell epitope from human heat-shock protein 60, an autoantigen involved in the pathogenesis of rheumatoid arthritis. Three APLs were designed from this epitope and it was demonstrated that these peptides induce the activation of T cells through their ability to modify cell cycle phase's distribution of CD4+T cells from RA patients. Also, IL-17, TNF-α and IL-10 levels were determined in PBMC from these patients. Unlike the wild-type peptide and the other two APLs, APL2 increased the IL-10 level and suppressed IL-17 secretion in these assays. Therapeutic effect of this APL in adjuvant arthritis (AA) and collagen-induced arthritis (CIA) models was also evaluated. Clinical score, histopathology, inflammatory and regulatory cytokine concentration were monitored in the animals. APL2 efficiently inhibited the progression of AA and CIA with a significant reduction of the clinical and histopathologic score. Therapeutic effect of APL2 on CIA was similar to that obtained with MTX; the standard treatment for RA. This effect was associated with a decrease of TNF-α and IL-17 levels. These results suggest that the therapeutic effect of APL2 is mediated in part by down-regulation of inflammatory cytokines and support the potential use of APL2 as a therapeutic drug in RA patients.
Databáze:	OpenAIRE
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