Few data are available on this item. Previously, Sander et al. [29] reported a fast disruption of intestinal barrier function in Caco-2 cells (after 4 h of exposure to gliadin peptic-tryptic digest)

that markedly involved Occludin, ZO-1 and E-cadherin. In our study, the events were not so rapid even if, in agreement with these authors, we also found that permeability, as measured by TER, increased immediately after gliadin addition reaching its maximum after 60 minutes. The differences in TJ expression between the two studies probably rely on the toxic agent administered. In fact, we used wheat gliadin instead of the peptic-tryptic (PT) digests that are known to have different modes of action in regard to their toxicity. PT treatment induces the production of alkenals MK-8776 manufacturer that in turn can modify the activity of membrane-associated proteins and enzymes [30]. The modifications in paracellular permeability went together with a rising selleck in the single and total buy SIS3 polyamine content that was evident and significant after 6 h of exposure. A clear role for polyamines at cellular and molecular levels in the gliadin-triggered damage of intestinal epithelia is still under debate. Regulation of brush border functions by spermidine and spermine has been suggested to be mediated by a transglutaminase-induced

incorporation of polyamines into membrane proteins [31]. Besides, it has been hypothesized that epithelial binding of gliadin peptides may occur in the form of IgA immune complexes which then translocate

across the epithelium [32]. This binding could represent powerful extraneous growth factors for the gut and, as a result, induce extensive proliferation and changes in the metabolism of epithelial cells via activation of second messenger pathways. These metabolic changes may release huge amounts of polyamines, mostly spermidine [33]. On the other hand, the increase in polyamine content probably results from increased cell proliferation during the repair phase of mucosal injury. In this context, polyamine levels could be regarded as markers of a hyperproliferative state in response to toxic effects of gliadin. This behavior by polyamines DAPT in vivo has already been reported during inflammation of intestine leading to derangement of the mucosa [34]. The second aim of the study was to investigate the possible effects on paracellular permeability and polyamine content following co-administration of viable L.GG, LGG-HK or its conditioned medium with gliadin. In previous experiments by our group, L.GG was proven to be effective in modulating cell proliferation and polyamine metabolism and biosynthesis also when its components (namely cytoplasm extracts and cell wall extracts) were tested, supporting the hypothesis that intact cells is not a pre-requisite for the L.GG protective effects [19, 20].