Nuclear factor- B activation promotes restitution of wounded intestinal epithelial monolayers

Egan, Laurence J., Ana de Lecea, Evan D. Lehrman, Gennett M. Myhre, Lars Eckmann, and Martin F. Kagnoff. Nuclear factorB activation promotes restitution of wounded intestinal epithelial monolayers. Am J Physiol Cell Physiol 285: C1028–C1035, 2003. First published June 25, 2003; 10.1152/ajpcell.00167.2003.—Epithelial restitution, the movement of wound-edge cells into an area of epithelial cell denudation, is an important early step in the ulcer healing process. Growth factors regulate epithelial restitution, yet little is known about the transcriptional pathways that mediate their effects on cell migration. The transcription factor nuclear factor (NF)B is a master regulator of the host inflammatory response that is activated in the epithelium in intestinal inflammation, which often accompanies epithelial injury. We hypothesized that NFB may be an important transcriptional regulator of epithelial restitution. In an in vitro model of scrape-wounded monolayers of nontransformed rat intestinal epithelial (RIE-1) cells, NFB was activated in epithelial cells at the wound edge. Blocking of NFB activation by either pharmacological or genetic approaches inhibited intestinal epithelial restitution. Moreover, scrape wounding activated the epidermal growth factor receptor (EGFR) in cells at the wound edge, and, importantly, inhibiting EGFR tyrosine kinase activity decreased scrape wound-induced NFB activation and cell migration. These results indicate a novel role of NFB activation in a signaling pathway important for restitution and healing of intestinal epithelia. To the extent NFB may have parallel functions in vivo, they also suggest a need for caution in the proposed use of NFB inhibitors for the treatment of conditions associated with inflammation and injury of intestinal and other mucosal surfaces.