Cellular alterations of mucosal integrity by ribotoxins: mechanistic implications of environmentally-linked epithelial inflammatory diseases

Specific ribosome-directed stressors have the capacity to damage 28S ribosomal RNA by interfering with its functioning during gene translation. This can lead to what has been called ribotoxic stress responses that are closely associated with various disease processes including epithelial inflammation in humans and domestic animals. Since the primary toxic actions of most ribotoxic stress agents are generally recognized to be the functional inhibition of global protein synthesis, highly dividing tissues including epithelia are the most susceptible targets of toxic insult. In the present study, responses in the mucosal barrier by acute and chronic exposure to ribosome-inactivating agents were reviewed in various experimental models. Specifically, the focus of this review will be on the regulation of mucosa-associated microbiota, epithelial pro-inflammatory insult, and epithelial integrity. The review aims at characterizing the mechanistic evidence of the ribotoxic stress-induced cellular responses and their implication as critical etiological factors of mucosa-associated diseases, in particular epithelial inflammatory disease.