Bronchitis, asthma, and cystic fibrosis, marked by inflammation and mucus hypersecretion, can be caused or exacerbated by airway pathogens or irritants including acrolein, an aldehyde present in tobacco smoke. To determine whether acrolein and inflammatory mediators alter mucin gene expression, steady-state mRNA levels of two airway mucins, MUC5AC and MUC5B, were measured (by RT-PCR) in human lung carcinoma cells (NCI-H292). MUC5AC mRNA levels increased after 0.01 nM acrolein, 10 µM prostaglandin E₂ or 15-hydroxyeicosatetraenoic acid, 1.0 nM tumor necrosis factor- (TNF-), or 10 nM phorbol 12-myristate 13-acetate (a protein kinase C activator). In contrast, MUC5B mRNA levels, although easily detected, were unaffected by these agonists, suggesting that irritants and associated inflammatory mediators increase mucin biosynthesis by inducing MUC5AC message levels, whereas MUC5B is constitutively expressed. When transcription was inhibited, TNF- exposure increased MUC5AC message half-life compared with control level, suggesting that transcript stabilization is a major mechanism controlling increased MUC5AC message levels. Together, these findings imply that irritants like acrolein can directly and indirectly (via inflammatory mediators) increase airway mucin transcripts in epithelial cells.

aldehyde; chronic obstructive pulmonary disease; cytokine; eicosanoids

This article has been cited by other articles:

				M. C. Rose and J. A. Voynow Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease Physiol Rev, January 1, 2006; 86(1): 245 - 278. [Abstract] [Full Text] [PDF]

				T. Gray, R. Coakley, A. Hirsh, D. Thornton, S. Kirkham, J.-S. Koo, L. Burch, R. Boucher, and P. Nettesheim Regulation of MUC5AC mucin secretion and airway surface liquid metabolism by IL-1{beta} in human bronchial epithelia Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L320 - L330. [Abstract] [Full Text] [PDF]

				Y. Kaneko, K. Yanagihara, M. Seki, M. Kuroki, Y. Miyazaki, Y. Hirakata, H. Mukae, K. Tomono, J.-i. Kadota, and S. Kohno Clarithromycin inhibits overproduction of muc5ac core protein in murine model of diffuse panbronchiolitis Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L847 - L853. [Abstract] [Full Text] [PDF]

				B. M. Fischer, J. G. Cuellar, M. L. Diehl, A. M. deFreytas, J. Zhang, K. L. Carraway, and J. A. Voynow Neutrophil elastase increases MUC4 expression in normal human bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, April 1, 2003; 284(4): L671 - L679. [Abstract] [Full Text] [PDF]

				J. G. Wagner, J. A. Hotchkiss, and J. R. Harkema Enhancement of Nasal Inflammatory and Epithelial Responses after Ozone and Allergen Coexposure in Brown Norway Rats Toxicol. Sci., June 1, 2002; 67(2): 284 - 294. [Abstract] [Full Text] [PDF]

				G. D. Leikauf, M. T. Borchers, D. R. Prows, and L. G. Simpson Mucin Apoprotein Expression in COPD* Chest, May 1, 2002; 121 (2009): 166S - 182S. [Abstract] [Full Text] [PDF]

				M. C. Rose, T. J. Nickola, and J. A. Voynow Airway Mucus Obstruction: Mucin Glycoproteins, MUC Gene Regulation and Goblet Cell Hyperplasia Am. J. Respir. Cell Mol. Biol., November 1, 2001; 25(5): 533 - 537. [Full Text] [PDF]

				J. G. Wagner, S. J. Van Dyken, J. A. Hotchkiss, and J. R. Harkema Endotoxin Enhancement of Ozone-Induced Mucous Cell Metaplasia Is Neutrophil-Dependent in Rat Nasal Epithelium Toxicol. Sci., April 1, 2001; 60(2): 338 - 347. [Abstract] [Full Text] [PDF]

				A. Choudhury, R. K. Singh, N. Moniaux, T. H. El-Metwally, J.-P. Aubert, and S. K. Batra Retinoic Acid-dependent Transforming Growth Factor-beta 2-mediated Induction of MUC4 Mucin Expression in Human Pancreatic Tumor Cells Follows Retinoic Acid Receptor-alpha Signaling Pathway J. Biol. Chem., October 20, 2000; 275(43): 33929 - 33936. [Abstract] [Full Text] [PDF]