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Interleukin-1beta regulates CFTR expression in human intestinal T84 cells
E G Cafferata1, A M González-Guerrico, L Giordano
1Instituto de Investigaciones Bioquímicas-Fundación Campomar (IIB, UBA, IIBBA, CONICET), Patricias Argentinas 435, 1405, Buenos Aires, Argentina.
Biochimica Et Biophysica Acta
|February 5, 2000
Summary
Interleukin-1beta (IL-1beta) influences cystic fibrosis transmembrane conductance regulator (CFTR) expression in T84 cells. Low IL-1beta doses increase CFTR, while higher doses inhibit it, involving protein kinase pathways.
Area of Science:
- Cellular Biology
- Genetics
- Immunology
Background:
- Cystic fibrosis is a genetic disorder caused by CFTR gene mutations.
- CFTR functions as a chloride channel, crucial for cellular function.
- The regulation of CFTR expression by extracellular factors is not well understood.
Purpose of the Study:
- To investigate the effect of interleukin-1beta (IL-1beta) on CFTR expression in human colonic T84 cells.
- To elucidate the signaling pathways involved in IL-1beta-mediated CFTR modulation.
Main Methods:
- Treatment of T84 cells with varying concentrations of IL-1beta.
- Analysis of CFTR mRNA and protein levels.
- Inhibition studies using protein kinase C (PKC) and protein tyrosine kinase (PTK) inhibitors.
- Assessment of de novo protein synthesis and mRNA stability.
Main Results:
- Low-dose IL-1beta (0.25 ng/ml) increased CFTR mRNA and protein expression.
- High-dose IL-1beta (≥1 ng/ml) inhibited CFTR mRNA and protein expression.
- PKC and PTK inhibitors blocked the stimulatory effect of IL-1beta, suggesting their involvement.
- Cycloheximide indicated de novo protein synthesis is required for upregulation.
- DRB suggested increased mRNA levels are not due to enhanced stability.
Conclusions:
- IL-1beta modulates both CFTR mRNA and protein levels in T84 cells.
- This cytokine is the first identified extracellular protein to upregulate CFTR gene expression.
- PKC and PTK signaling pathways, along with de novo protein synthesis, are implicated in IL-1beta's effect on CFTR.