Peptide-based vaccination against OPN integrin binding sites does not improve cardio-metabolic disease in mice.
Immunol Lett
; 179: 85-94, 2016 11.
Article
en En
| MEDLINE
| ID: mdl-27639826
ABSTRACT
Obesity causes insulin resistance via a chronic low-grade inflammation. This inflammation is characterized by elevated pro-inflammatory markers and macrophage accumulation in the adipose tissue (AT). AT inflammation is a key factor causing insulin resistance and thus type 2 diabetes, both linked to atherosclerotic cardiovascular disease. Osteopontin (OPN), a well-known inflammatory cytokine, is involved in obesity-linked complications including AT inflammation, insulin resistance, atherosclerosis and CVD. During inflammation, OPN is proteolytically cleaved by matrix metalloproteinases or thrombin leading to increased OPN activity. Therefore, OPN provides a new interesting target for immunological prevention and treatment of obesity-associated diseases. The aim of our study was to evaluate peptide-based vaccines against integrin binding sites of OPN and to examine whether these active immunotherapies are functional in reducing metabolic tissue inflammation, insulin resistance, and atherosclerosis in a cardio-metabolic (Ldlr-/- mice) and a diet-induced obesity model (WT mice). However, atherosclerosis, insulin resistance and AT inflammation were not diminished after treatment with OPN-derived peptides in murine models. Lack of efficacy was based on a failure to induce antibodies capable to bind epitopes in the context of functional OPN protein. In conclusion, our data point to unexpected challenges in the immunotherapeutic targeting of adhesive motives, such as RGD containing sequences, on endogenous proteins.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Sitios de Unión
/
Integrinas
/
Osteopontina
/
Cardiopatías
/
Enfermedades Metabólicas
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Immunol Lett
Año:
2016
Tipo del documento:
Article
País de afiliación:
Austria