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IL-9 Modulated MUC4 Gene and Glycoprotein Expression in Airway Epithelial Cells

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Abstract

Compromised epithelial cell integrity is a common feature associated with chronic lung inflammatory states such as asthma. While epithelial cell damage is largely due to sustained effects of inflammatory mediators localized to airways, the subsequent process of epithelial cell differentiation is attributed to members of the transmembrane receptor tyrosine kinase family called the ErbB’s. MUC4, a large molecular weight membrane-bound glycoprotein, has recently been identified as a potential ligand for the ErbB-2 receptor. In this study, we investigated the possible role of interleukin-9 (IL-9), a Th2 cytokine, on MUC4 expression using a lung cancer cell line, NCI-H650. We determined that IL-9 up-regulates MUC4 expression in a time and concentration-dependent fashion. Nuclear run-on assays indicated transcriptional regulation of MUC4 while no post-transcriptional mRNA stabilization was observed by actinomycin D chase experiments. IL-9 also increased MUC4 glycoprotein expression as determined by Western blots using a monoclonal antibody specific for a non-tandem repeat region on ASGP-2 region of MUC4. Furthermore, a JAK3-selective inhibitor 4-(4′-hydroxyphenyl) amino-6, 7-dimethoxyquinazoline (WHI-P131), substantially reduced IL-9-induced MUC4 mRNA expression in a dose-dependent fashion. These results implicate a potential role for IL-9 upon MUC4 expression in human airway epithelial cells.

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Acknowledgements

This study was supported in part by National Institute of Health grant HL34012. The authors thank Dr. S. Terence Dunn, Department of Pathology, OUHSC, for his help in preparation of this manuscript.

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Authors and Affiliations

  1. College of Pharmacy, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Oklahoma City, OK, 73190, USA

    Gautam Damera, Baoyun Xia & Goverdhan P. Sachdev

  2. College of Medicine, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Oklahoma City, OK, , 73104, USA

    Hanumatha R. Ancha

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  1. Gautam Damera
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  2. Baoyun Xia
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  3. Hanumatha R. Ancha
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  4. Goverdhan P. Sachdev
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Correspondence to Goverdhan P. Sachdev.

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Damera, G., Xia, B., Ancha, H.R. et al. IL-9 Modulated MUC4 Gene and Glycoprotein Expression in Airway Epithelial Cells. Biosci Rep 26, 55–67 (2006). https://doi.org/10.1007/s10540-006-9000-5

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