The accumulation of leukocytes in various organs contributes to the pathogenesis of a number of human autoimmune diseases such as asthma, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, hepatitis C, and multiple sclerosis.(1) The inflammatory processes leading to tissue damage and disease are mediated in part by the α4β1 integrins expressed on the leukocyte cell surface. These glycoprotein receptors modulate cell adhesion via interaction with their primary ligands VCAM e MAdCAM, expressed in the affected tissue. Binding results in firm adhesion of the leukocytes to the vessel wall followed by entry into the affected tissue.(2) Elevated CAM expression in various organs has been linked with several autoimmune diseases. In addition, increasing evidence points to important causative links between inflammation and cancer; in fact, the α4β1 integrin is also involved in the formation of new cancer blood vessels.(3) In this work we discuss a library of peptidomimetic inhibitors of α4β1 integrin based on a rigid central scaffold, β-amino acid residues, and partially modified retro-inverso sequence. Peptidomimetic integrin antagonists capable of inhibiting the adhesion of leucocytes to their ligands might represent a new approach for treatment of human inflammatory diseases and cancer, alternative to the use of monoclonal antibodies. The pharmacological characterization has been performed by the cell-adhesion inhibition (Jurkat) and SPA assays. The animal model allowed us to study the effect of the compounds in reducing inflammation and allergic reactions. Main mediators of these two phenomena are eosinophils (Eol-1 cell line), particular cells of the immune system, of which we are going to study the presence or not in samples obtained from the animals

NEW PEPTIDOMIMETIC α4β1-INTEGRIN ANTAGONISTS FOR REDUCING INFLAMMATION AND ALLERGIC REACTIONS

GRECO, ARIANNA;DE MARCO, ROSSELLA;TOLOMELLI, ALESSANDRA;VIOLA, ANGELO;SPAMPINATO, SANTI MARIO;BAIULA, MONICA;DATTOLI, SAMANTHA DEIANIRA;GENTILUCCI, LUCA
2012

Abstract

The accumulation of leukocytes in various organs contributes to the pathogenesis of a number of human autoimmune diseases such as asthma, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, hepatitis C, and multiple sclerosis.(1) The inflammatory processes leading to tissue damage and disease are mediated in part by the α4β1 integrins expressed on the leukocyte cell surface. These glycoprotein receptors modulate cell adhesion via interaction with their primary ligands VCAM e MAdCAM, expressed in the affected tissue. Binding results in firm adhesion of the leukocytes to the vessel wall followed by entry into the affected tissue.(2) Elevated CAM expression in various organs has been linked with several autoimmune diseases. In addition, increasing evidence points to important causative links between inflammation and cancer; in fact, the α4β1 integrin is also involved in the formation of new cancer blood vessels.(3) In this work we discuss a library of peptidomimetic inhibitors of α4β1 integrin based on a rigid central scaffold, β-amino acid residues, and partially modified retro-inverso sequence. Peptidomimetic integrin antagonists capable of inhibiting the adhesion of leucocytes to their ligands might represent a new approach for treatment of human inflammatory diseases and cancer, alternative to the use of monoclonal antibodies. The pharmacological characterization has been performed by the cell-adhesion inhibition (Jurkat) and SPA assays. The animal model allowed us to study the effect of the compounds in reducing inflammation and allergic reactions. Main mediators of these two phenomena are eosinophils (Eol-1 cell line), particular cells of the immune system, of which we are going to study the presence or not in samples obtained from the animals
Abstract
1
1
A. Greco; R. De Marco; A. Tolomelli; A. Viola; S. Spampinato; M. Baiula; S. Dattoli; L. Gentilucci
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/396219
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact