APL-2, an altered peptide ligand derived from heat-shock protein 60, induces interleukin-10 in peripheral blood mononuclear cell derived from juvenile idiopathic arthritis patients and downregulates the inflammatory response in collagen-induced arthritis model

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by autoimmune arthritis of unknown cause with onset before age of 16 years. Methotrexate provides clinical benefits in JIA. For children who do not respond to methotrexate, treatment with anti-tumor necrosis facto...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical and experimental medicine Vol. 15; no. 1; pp. 31 - 39
Main Authors:	Lorenzo, Norailys, Cantera, Dolores, Barberá, Ariana, Alonso, Amaris, Chall, Elsy, Franco, Lourdes, Ancizar, Julio, Nuñez, Yanetsy, Altruda, Fiorella, Silengo, Lorenzo, Padrón, Gabriel, del Carmen Dominguez, Maria
Format:	Journal Article
Language:	English
Published:	Cham Springer International Publishing 01-02-2015 Springer Nature B.V
Subjects:	Adolescent Animals Antirheumatic Agents - pharmacology Arthritis Arthritis, Experimental - drug therapy Arthritis, Experimental - genetics Arthritis, Experimental - immunology Arthritis, Experimental - pathology Arthritis, Juvenile - genetics Arthritis, Juvenile - immunology Arthritis, Juvenile - pathology Autoantigens - chemistry Autoantigens - pharmacology Chaperonin 60 - chemistry Chaperonin 60 - genetics Chaperonin 60 - immunology Child Child, Preschool Collagen Gene Expression Regulation Hematology Humans Interferon-gamma - biosynthesis Interferon-gamma - secretion Interleukin-10 - biosynthesis Interleukin-10 - secretion Interleukin-17 - antagonists & inhibitors Interleukin-17 - biosynthesis Interleukin-17 - secretion Internal Medicine Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - pathology Medicine Medicine & Public Health Methotrexate - pharmacology Mice Mitochondrial Proteins - chemistry Mitochondrial Proteins - genetics Mitochondrial Proteins - immunology Oncology Original Article Peptides Peptides - chemical synthesis Peptides - pharmacology Peripheral Tolerance Primary Cell Culture Proteins Signal Transduction Sulfasalazine - pharmacology Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - secretion Tolerance Altered peptide ligand Interleukin-10 Collagen-induced arthritis Juvenile idiopathic arthritis
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by autoimmune arthritis of unknown cause with onset before age of 16 years. Methotrexate provides clinical benefits in JIA. For children who do not respond to methotrexate, treatment with anti-tumor necrosis factor (TNF)-α is an option. However, some patients do not respond or are intolerant to anti-TNF therapy. Induction of peripheral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases. We aimed to evaluate the potentialities of two altered peptide ligands (APLs) derived from human heat-shock protein 60, an autoantigen involved in the pathogenesis of autoimmune arthritis, in JIA patients. Interferon (IFN)-γ, TNF-α and interleukin (IL)-10 levels were determined in ex vivo assays using peripheral blood mononuclear cells (PBMC) from these patients. Wild-type peptide and one of these APLs increased IFN-γ and TNF-α levels. Unlike, the other APLs (called APL2) increased the IL-10 level without affecting IFN-γ and TNF-α levels. On the other hand, APL2 induces a marked activation of T cells since it transforms cell cycle phase’s distribution of CD4+ T cells from these patients. In addition, we evaluated the therapeutic effect of APL2 in collagen-induced arthritis model. Therapy with APL2 reduced arthritis scores and histological lesions in mice. This effect was associated to a decrease in TNF-α and IL-17 levels. These results indicate a therapeutic potentiality of APL2 for JIA.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1591-9528 1591-8890 1591-9528
DOI:	10.1007/s10238-014-0273-x