Cytokine regulation of CD44 expression on rat intestinal epithelial cells

CD44 comprises a family of type I transmembrane glycoproteins that is expre ssed on a wide range of cells including those of epithelial, lymphoid and m yeloid lineage. Although expression of CD44 in the small intestine is typic ally localised in the crypts of Lieberkuhn, we have reported the expression of CD44 on mature, intestinal villus epithelial cells during the developme nt of small bowel allograft rejection. The mechanisms underlying CD44 up-re gulation are unknown, although it may be influenced by localised cytokine p roduction. This study used flow cytometry to assess the effects of recombin ant IFN-gamma and TNF-alpha on CD44 expression and hyaluronan binding by th e rat small intestinal epithelial cell lines, RIE and IEC 6. IFN-gamma upre gulated CD44 expression on RIE (155% of unstimulated control) and IEC 6 (20 9% of unstimulated control) cells, whereas TNF-alpha had no effect. IFN-gam ma had no qualitative effect on CD44, as binding of the ubiquitously expres sed extracellular matrix polysaccharide hyaluronan was unchanged. RIE and I EC 6 cells expressed the 82 kDa and 130 kDa major isoforms of CD44, however cytokine stimulation did not affect the expression of these, nor did stimu lation induce the expression of other variants. In summary, these findings demonstrate that CD44 expression by intestinal epithelial cells can be regu lated by cytokines, yet their ability to bind hyaluronan and the isoform of the expressed CD44 remains unaltered. It appears that localised inflammato ry conditions and cytokine production may modify epithelial cell expression of CD44, however the physiological role for such a response has yet to be elucidated.