Regulation of intestinal epithelial cell function by IL-10: implications for the regulation of KG and the transcription factor C/EBP-,β

The host response to the massive antigenic load in the intestinal lumen is regulated by cytokines that select for protective immunity that is not associated with excessive amounts of inflammation. The appearance of chronic intestinal inflammation in IL-10 knock-out mice suggests IL-10 may inhibit adverse responses to luminal antigen. The purpose of these experiments was to determine if IL-10 binds to and directly regulates intestinal epithelial cell function. Using flow cytometry, IL-10 binding was observed on intestinal epithelial cell lines as well as freshly isolated enterocytes. This binding appeared specific since it could be blocked by neutralizing antibodies to IL-10. In addition, the binding of iodinated IL-10 was inhibited by an excess of "cold" ligand- Amplification of mRNA by RT-PCR showed that epithelial cells also expressed mRNA for the IL-10 receptor. The m urine intestinal epithelial cell line (Mode-K) also expressed mRNA for KG, a chemokine capable of recruiting neutrophils. The expression of KC was associated with the presence of mRNA for C/EBP-/3, a transcription factor that putatively regulates KC. In addition, raRNA for both KC and C/EBP-0 was detected at increased levels in the large intestine of IL-10-deficient mice. These results suggest that IL-10 binds to a specific receptor on gastrointestinal epithelial cells and may play an important role in the cytokine network that determines the magnitude of the inflammatory response in the digestive tract.