Wilhelm, C. et al. Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection.
Treatment with KGF or the synthetic glucocorticoid dexamethasone alleviated LT-mediated barrier damage significantly, thus providing a potential therapeutic option for anthrax victims.
A direct comparison of mannitol infusion and AAV-mediated barrier modulation was not performed during the course of this study given the disparity between the two approaches.
One possible interpretation of the results is that structural barrier defect caused y EPI mutations results in compensatory immune-mediated barrier defense that confers protection.
It should be stressed that EPEC-mediated barrier dysfunction and inhibition of IL-8 secretion are unlinked, as the former (Dean and Kenny, 2004) but not the latter is dependent on LEE-encoded Intimin protein (Fig. 3).
Taken together, this study shows that EPEC-mediated barrier disruption requires Intimin (Canil et al., 1993; Dean and Kenny, 2004), Tir (this study) and the cooperative actions of Map and EspF (McNamara et al., 2001; Dean and Kenny, 2004).
Furthermore, our results argue for a novel mode of action of natalizumab at the BBB, where it may partially protect brain endothelial cells from a sVCAM-1-mediated barrier breakdown.
The clear absence of increased IL-8 secretion in response to EPEC-mediated barrier dysfunction, which also allows access of host membrane proteins to the apical surface (Muza-Moons et al., 2003), is suggestive of a defect in inducing IL-8 secretion downstream of TLR-5/flagellin interaction.
While the outer membrane protein Intimin is essential for EPEC-mediated barrier disruption (Dean and Kenny, 2004), the contribution of its primary receptor Tir is unclear with previous studies reporting essential (Muza-Moons et al., 2003; Miyake et al., 2005) or non-essential (Dean and Kenny, 2004) roles.
