Regulation of IL-1beta-mediated MUC2 gene in NCI-H292 human airway epithelial cells.
This study demonstrates for the first time the effects of IL-1beta on the regulation of protein production as well as MUC2 gene transcription in cultured human airway epithelial cells. The effect of IL-1beta on the regulation of MUC2 protein was determined by flow cytometric analysis. The expression level of MUC2 induced by IL-1beta increased in a dose-dependent manner. MUC2 transcripts were detected after 2 h of exposure to IL-1beta and reached maximal level after 8 h. Actinomycin D experiments indicated that the IL-1beta-mediated MUC2 expression was controlled by transcriptional regulation. Both RT-PCR and FACS analysis showed that budesonide concomitantly attenuated IL-1beta mediated MUC2 gene as well as protein production levels. Use of the glucocorticoid receptor antagonist, RU-486, restored the inhibitory effect of budesonide on the IL-1beta-mediated MUC2 protein as well as gene. The data suggest that IL-1beta up-regulates MUC2 gene by transcriptional regulation and that budesonide suppresses the IL-1beta-medicated MUC2 expression via decreased transcriptional activation.
Kim
Y D
YD
Department of Otorhinolaryngology, Yeungnam University, Taegu, 705-717, South Korea.
Kwon
E J
EJ
Kwon
T K
TK
Baek
S H
SH
Song
S Y
SY
Suh
J S
JS
D001993:Bronchodilator Agents / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology; D002469:Cell Separation; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008168:Lung / Q000166:cytology*; D015735:Mifepristone / Q000494:pharmacology; D055262:Mucin-2; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D001993:Bronchodilator Agents; D006727:Hormone Antagonists; D007375:Interleukin-1; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D019384:Nucleic Acid Synthesis Inhibitors; D003609:Dactinomycin; D015735:Mifepristone; D019819:Budesonide