EPITHELIAL-CELLS SECRETE THE CHEMOKINE INTERLEUKIN-8 IN RESPONSE TO BACTERIAL ENTRY

Bacterial invasion of mucosal surfaces results in a rapid influx of po lymorphonuclear leukocytes. The chemotactic stimulus responsible for t his response is not known. Since epithelial cells are among the first cells entered by many enteric pathogens, we investigated the ability o f epithelial cells to provide an early signal for the mucosal inflamma tory response through the release of chemotactic cytokines. As shown h erein, the chemokine interleukin-8 (IL-8), a potent chemoattractant an d activator of polymorphonuclear leukocytes, was secreted by intestina l and cervical epithelial cells in response to bacterial entry. Moreov er, a variety of different bacteria, including those that remain insid e phagosomal vacuoles, e.g., Salmonella spp., and those that enter the cytoplasm, e.g., Listeria monocytogenes, stimulated this response. In creased IL-8 mRNA levels could be detected within 90 min after infecti on. Neither bacterial lipopolysaccharide nor noninvasive bacteria, inc luding Escherichia coli and Enterococcus faecium, induced an IL-8 resp onse. Moreover, tumor necrosis factor alpha, which is known to be expr essed by some epithelial cells, was not detected in the culture supern atants after bacterial entry, and addition of anti-tumor necrosis fact or alpha antibodies had no effect on the IL-8 response following bacte rial entry. These data suggest the novel concept that epithelial cells serve as an early signaling system to host immune and inflammatory ce lls in the underlying mucosa following bacterial entry.