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

Biochim Biophys Acta. 2000 Feb 21;1500(2):241-8. doi: 10.1016/s0925-4439(99)00105-2.

Abstract

Cystic fibrosis is an autosomal recessive genetic disease, produced by a mutation in the CFTR gene that impairs its function as a chloride channel. In this work, we have examined the effects of interleukin-1beta (IL-1beta) on the expression of CFTR in human colonic T84 cells. Treatment of T84 cells with IL-1beta (0.25 ng/ml) for 4 h resulted in an increased CFTR expression (mRNA and protein). However, higher doses of IL-1beta (1 ng/ml and over) produced inhibition of CFTR mRNA and protein expression. The protein kinase C (PKC) inhibitors H7 (50 microM) and GF109203X (1 microM) inhibited the stimulatory effect of IL-1beta. Similar effects were seen in the presence of the protein tyrosine kinase (PTK) inhibitors genistein (60 microM) and herbymicin A (2 microM). These results suggest that some PKC isoform(s) and at least a PTK might be involved in the CFTR up-regulation induced by IL-1beta. The repression of CFTR up-regulation by cycloheximide (35.5 microM) suggests the participation of a de novo synthesized protein. Results obtained by using the RNA polymerase II inhibitor DRB (78 microM), suggest that the increased mRNA levels seen after IL-1beta treatment are not due to an increased stability of the message. We conclude that the CFTR mRNA and protein levels are modulated by IL-1beta, this cytokine being the first extracellular protein known to up-regulate CFTR gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Adenocarcinoma / pathology
  • Benzoquinones
  • Cell Line
  • Colon / drug effects*
  • Colon / metabolism
  • Colonic Neoplasms / pathology
  • Cycloheximide / pharmacology
  • Cystic Fibrosis Transmembrane Conductance Regulator / biosynthesis*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Enzyme Inhibitors / pharmacology
  • Genistein / pharmacology
  • Humans
  • Indoles / pharmacology
  • Interleukin-1 / pharmacology*
  • Lactams, Macrocyclic
  • Maleimides / pharmacology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Phosphorylation / drug effects
  • Protein Kinase C / antagonists & inhibitors
  • Protein Processing, Post-Translational / drug effects
  • Protein Synthesis Inhibitors / pharmacology
  • Quinones / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Rifabutin / analogs & derivatives
  • Signal Transduction / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Up-Regulation / drug effects*

Substances

  • Benzoquinones
  • CFTR protein, human
  • Enzyme Inhibitors
  • Indoles
  • Interleukin-1
  • Lactams, Macrocyclic
  • Maleimides
  • Neoplasm Proteins
  • Protein Synthesis Inhibitors
  • Quinones
  • RNA, Messenger
  • RNA, Neoplasm
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Rifabutin
  • herbimycin
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Cycloheximide
  • Genistein
  • Protein Kinase C
  • bisindolylmaleimide I
  • Tetradecanoylphorbol Acetate