%0 Journal Article
%T Phage Display Screening for Tumor Necrosis Factor-¦Á-Binding Peptides: Detection of Inflammation in a Mouse Model of Hepatitis
%A Coralie Sclavons
%A Carmen Burtea
%A S¨¦bastien Boutry
%A Sophie Laurent
%A Luce Vander Elst
%A Robert N. Muller
%J International Journal of Peptides
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/348409
%X TNF-¦Á is one of the most abundant cytokines produced in many inflammatory and autoimmune conditions such as multiple sclerosis, chronic hepatitis C, or neurodegenerative diseases. These pathologies remain difficult to diagnose and consequently difficult to treat. The aim of this work is to offer a new diagnostic tool by seeking new molecular probes for medical imaging. The target-specific part of the probe consists here of heptameric peptides selected by the phage display technology for their affinity for TNF-¦Á. Several affinity tests allowed isolating 2 peptides that showed the best binding capacity to TNF-¦Á. Finally, the best peptide was synthesized in both linear and cyclic forms and tested on the histological sections of concanavalin-A-(ConA-)treated mice liver. In this well-known hepatitis mouse model, the best results were obtained with the cyclic form of peptide 2, which allowed for the staining of inflamed areas in the liver. The cyclic form of peptide 2 (2C) was, thus, covalently linked to iron oxide nanoparticles (magnetic resonance imaging (MRI) contrast agent) and tested in the ConA-induced hepatitis mouse model. The vectorized nanoparticles allowed for the detection of inflammation as well as of the free peptide. These ex vivo results suggest that phage display-selected peptides can direct imaging contrast agents to inflammatory areas. 1. Introduction Tumor necrosis factor alpha (TNF- ) is a proinflammatory cytokine produced in many inflammatory and autoimmune diseases such as rheumatoid arthritis, Crohn¡¯s disease, multiple sclerosis, or chronic hepatitis C [1, 2]. TNF- is produced by different cell types including macrophages, monocytes, T-cells, smooth muscle cells, adipocytes, and fibroblasts. This cytokine is also implicated in the diseases of the central nervous system like Alzheimer¡¯s and Parkinson¡¯s diseases [3], where it can be produced by several cell populations, including microglia, astrocytes, endothelial cells, Th1 lymphocytes and neurons. Mature TNF- is secreted as a 157-amino acid form [4] with a molecular weight of 17£¿kDa [5]. Before being released from cells, TNF- is anchored in the plasma membrane as a 26£¿kDa precursor containing both hydrophobic and hydrophilic regions [6]. The 17£¿kDa form of TNF- is excised from the integral transmembrane precursor by proteolytic cleavage mediated by the tumor necrosis factor alpha converting enzyme (TACE) [7]. Soluble and transmembrane TNF- are produced by cells as homotrimers that bind to two kinds of receptors, TNF-RI and TNF-RII (tumor necrosis factor receptor type I, p55; type II,
%U http://www.hindawi.com/journals/ijpep/2013/348409/