Inhibition of abnormal intestinal epithelial permeability by targeted gene therapy

The gastrointestinal (GI) epithelium is vital for absorption of nutrients and maintenance of a selective barrier between the external and internal environments. The intestinal epithelial cells (IECs) are fundamental to these functions and are also important components of the mucosal immune system. Disease, trauma, or gram-negative infection can rapidly disrupt GI homeostasis and result in intestinal epithelial barrier disruptions, indicated by measurable increases in intestinal permeability (IP). These effects are often associated with activation of the transcription factor, Nuclear Factor kappa B (NF-κB), and can ultimately lead to sepsis or multiple organ dysfunction. The results of the present study suggest that such IP increases in vivo may be mediated by TNF-α at the basolateral surface of IECs, in an NF-κB-dependent fashion, and also support the therapeutic potential of intestinal gene therapy using the NF-κB inhibitory protein (IκB) to modulate the negative effects of NF-κB on intestinal barrier function.