Interleukin-1 beta regulates CFTR expression in human intestinal T84 cells

Cystic fibrosis is an autosomal recessive genetic disease, produced by a mu tation in the CFTR gene that impairs its function as a chloride channel. In this work, Eve have examined the effects of interleukin-1 beta (IL-1 beta) on the expression of CFTR in human colonic T84 cells. Treatment of T84 cel ls with IL-1 beta (0.25 ng/ml) for 4 h resulted in an increased CFTR expres sion (mRNA and protein). However, higher doses of IL-1 beta (1 ng/ml and ov er) produced inhibition of CFTR mRNA and protein expression. The protein ki nase C (PKC) inhibitors H7 (50 mu M) and GF109203X (1 mu M) inhibited the s timulatory effect of IL-1 beta. Similar effects were seen in the presence o f the protein tyrosine kinase (PTK) inhibitors genistein (60 mu M) and herb ymicin A (2 mu M). These results suggest that some PKC isoform(s) and at le ast a PTK might be involved in the CFTR upregulation induced by IL-1 beta. The repression of CFTR up-regulation by cycloheximide (35.5 mu M) suggests the participation of a de novo synthesized protein. Results obtained by usi ng the RNA polymerase II inhibitor DRB (78 mu M), suggest that the increase d mRNA levels seen after IL-1 beta treatment are not due to an increased st ability of the message. We conclude that the CFTR mRNA and protein levels a re modulated by IL-1 beta, this cytokine being the first extracellular prot ein known to upregulate CFTR gene expression. (C) 2000 Elsevier Science B.V . All rights reserved.