The Claudin family of TJ proteins regulates the epithelial paracellular permeability. Claudins are 20- to 27-kDa proteins containing 2 extracellular www.selleckchem.com/products/lazertinib-yh25448-gns-1480.html loops with variably charge
aminoacid residues among family members and short intracellular tails [8]. In intestinal epithelial cells, Claudin-1 expression is associated with enhancement of epithelial barrier function [9] and it is found to be decreased in both intestinal and extraintestinal diseases [10]. Among the several substances involved in the IP control, polyamines play a crucial role. These polycationic compounds are ubiquitous short-chain aliphatic amines present in all the eukaryotic cells studied and regulate cell proliferation and differentiation [11]. Polyamines are also involved in the expression and functions of intercellular junction proteins, as well as in maintenance of intestinal epithelial buy Eltanexor integrity [12]. With their positive charges, polyamines can form bridges between distant negative charges, resulting in
unique effects on permeability. The action of polyamines in modulating IP to different-sized markers generally seems to depend on their concentration [13]. Spermidine appears to enhance mucosal permeability to macromolecules at lower concentration PD0332991 cell line (1 mM), as compared to putrescine (10 mM). The protective effect of polyamines on the in vitro toxicity of gliadin peptides has been related to their effect on the functions of intestinal brush border or intracellular membranes involved in the handling of gliadin and initial studies suggested that amines could act as transglutaminase Oxymatrine amino donor substrates in the intestinal metabolism of gliadin peptides [14]. However, little is still known about the direct action of gliadin on the levels of polyamines in in vitro
cell conditions. At present, a strict, lifelong gluten-free diet (GFD) is the only CD treatment. Therefore, alternative strategies for treating CD are being hypothesized including agents that are able to counteract the gluten induced damage on epithelial mucosa. Probiotic bacteria have been shown to preserve the intestinal barrier promoting its integrity both in vitro and in vivo[15, 16]. Besides, different probiotic strains may show promising abilities in inhibiting gliadin-induced toxic effects [17] and a particular lactobacillus strain, the Lactobacillus rhamnosus GG (ATCC 53103) (L.GG), has shown properties in the prevention and treatment of different gastrointestinal diseases [18]. L.GG is one of the clinically best-studied probiotic organisms and displays very good in vitro adherence to epithelial cells and mucus. In previous studies by our group this strain, when tested as both viable and heat inactivated bacteria as well as homogenate and cytoplasm extracts, has also been demonstrated in vitro to significantly affect cell proliferation and polyamine metabolism [19, 20].