High-level expression of I kappa B-beta in the surface epithelium of the colon: in vitro evidence for an immunomodulatory role

The intestinal epithelium is spatially segregated into two compartments, on e containing undifferentiated cells in a proliferative state and one,vith n on-proliferative differentiated cells, Although this epithelium can produce many immune-modulatiug substances, emerging evidence suggests that the dif ferentiated cell compartment is less immune responsive. Indeed, it is the d ifferentiated cellular compartment that represents the interface between th e highly antigenic luminal environment and the mucosal immune system. The N F-kappa B/rel family of transcriptional activators play a critical role in regulating the inflammatory response by activating a wide variety of immune -modulatiug genes. These transcription factors are maintained in an inactiv e state in the cytoplasmic compartment by interaction with inhibitory prote ins of the I kappa B family. In this study we show by immunohistochemistry that I kappa B-beta is expressed at high levels specifically in the differe ntiated surface epithelium of the colonic mucosa. Using a naturally occurri ng compound found in the colon of vertebrates, butyrate, we provide evidenc e in an intestinal cell Line that alteration of I kappa B-beta expression c an modulate the transcriptional activation of the interleukin-8 (IL-8) gene by preventing the nuclear translocation of NF-kappa B proteins. Therefore, the expression of I kappa B-beta in the differentiated surface epithelium of the colon may help these cells act as an immunological barrier to preven t activation of the mucosal immune system.