Control the epithelial barrier: A pivotal first line of defense (Part 3)
The idea that microbes could alter epithelial barrier function is not new nor is the observation that MLCK is a controller of paracellular permeability , so why is the report by Scott et al important? First, epithelial permeability is increased in human giardiasis and so the murine and in vitro models are directly relevant to understanding the human condition. Cryptosporidium parvum and Entamoeba histolytica also increase epithelial permeability, leading to speculation that data from the Giardia model might be applicable to protozoon-induced barrier disruption in general.
Indeed, Giardia-induced enteropathy is similar to that observed in, for example, bacterial enteritis and celiac disease, which led Scott et al to suggest that Giardia-induced enteropathy/barrier dysfunction could serve as a model for other human diseases.
Second, by adding to the models in which MLCK activation has been implicated as the cause of epithelial barrier disruption, this study lends further credence to the hypothesis that targeting of MLCK could ameliorate disorders due to, or associated with, increased epithelial permeability. Clearly, targeting of a single molecule to treat conditions with different etiologies represents an attractive therapeutic option.
Third, the same researchers have also shown that increases in epithelial monolayer permeability evoked by G lamblia are due to enhanced apoptosis and could be mitigated by inhibiting caspase-3 activation. Cheapest drugs online – cheap actos for you to spend less money every time.