Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria

Abstract

Bacterial infection of the lung is associated with mucin overproduction. In partial explanation of this phenomenon, we recently reported that supernatant from the Gram-negative organism Pseudomonas (P.) aeruginosa contained an activity that upregulated transcription of the MUC 2 mucin gene [J.-D. Li, A. Dohrman, M. Gallup, S. Miyata, J. Gum, Y. Kim, J. Nadel, A. Prince, C. Basbaum, Transcriptional activation of mucin by P. aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease, Proc. Natl. Acad. Sci. U.S.A., 94 (1997) 967-972]. The purpose of the present study was to determine whether mucin genes other than MUC 2 are so regulated and whether Gram-positive organisms also contain mucin stimulatory activity. Results from in situ hybridization and RNase protection assays showed that P. aeruginosa upregulates MUC 5AC as well as MUC 2 in both bronchial explants and cultured airway epithelial cells. The upregulation of both genes by P. aeruginosa can be mimicked by lipopolysaccharide (LPS) and can be blocked by the tyrosine kinase inhibitor genistein. In addition, both genes are upregulated by a variety of Gram-positive as well as Gram-negative organisms showing the same rank order of potency. These data indicate the existence of a general mechanism by which epithelial cells respond to the presence of bacteria by increasing mucin synthesis.

Tumor necrosis factor α-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells

“…PA infection in airways is a major cause of mucin overproduction. PA sup and its major component, LPS, have been reported to cause MUC5AC expression in airway epithelial cells by means of EGFR phosphorylation (15,16). However, the mechanism by which PA sup and LPS cause EGFR activation was previously unknown.…”

“…In studies of PMA, cells were treated with PMA (10 ng͞ml) for 1 h. Then the cells were washed three times with serum-free medium and cultured for another 24 h in serum-free medium with the same concentrations of inhibitors as in the pretreatment period. In studies of PA sup, PA strain PAO1 was grown in M9 medium, and a cell-free culture supernatant (PA sup) was obtained (15,16). Cells were incubated with PA sup (1:8 dilution in medium containing 10% FCS) or LPS (from PA; 10 g͞ml in medium containing 10% FCS) for 24 h with or without inhibitors.…”

Airway epithelial cell signaling in response to bacterial pathogens

“…74 Bacterial components such as flagellin bind to mucin [75][76][77] and are cleared by the mucociliary escalator. Mucin concentration in broncoalveolar lavage is increased in response to LPS and flagella, and MUC5A gene expression is upregulated by LPS and Gram-positive and Gram-negative bacteria 78 as well as pro-inflammatory chemokines and cytokines expressed by airway epithelial cells. 79 MUC2 expression is also increased in response to P. aeruginosa LPS and flagellin, 80,81 S. aureus lipoteichoic acid 82 and H. influenzae 83 by signaling cascades that share common elements with those induced by TLRs.…”

Sequence of the 5′-flanking region and promoter activity of the human mucin gene MUC5B in different phenotypes of colon cancer cells

“…A TATA box is located at k23\k29 of the transcription start site and putative binding sites for Sp1, activator protein (AP)-2, glucocorticoid receptor element (GRE), NF-κB as well as a CACCC box were found within the promoter [20]. MUC5AC transcription is activated when bronchial ex-plants, airway epithelial cells (NCIH292) or colon cancer cells (HM3) are exposed to P. aeruginosa or its exoproducts in cell-free supernatants.…”