MUC1 modulates gastric epithelial immune response to bacteria or inflammatory stimuli

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Published: 2012-12-14
DOI: https://doi.org/10.18051/UnivMed.2012.v31.141-150
Keywords:
MUC1, epithelial cells, pathogen, inflammation

Main Article Content

Shofyatul Y. Triyana
Griffith University, Brisbane, Australia
Yong H. Sheng
Immunity, Infection and Inflammation Program, Mater Medical Research Institute and University of Queensland, Brisbane, Australia
Michael McGuckin
Immunity, Infection and Inflammation Program, Mater Medical Research Institute and University of Queensland, Brisbane, Australia

Abstract

BACKGROUND Cell surface mucin glycoproteins are expressed on the mucosal surface. One of these cell surface mucins is mucin-1 (MUC1), which plays a role as a physical barrier and limits inflammation. However, its functional role in modulating responses to pathogens, particularly with respect to intracellular signaling, needs to be investigated. Therefore, the aim of this study was to characterize the modulation of responses of human gastric epithelial cells by MUC1 to common mucosal pathogens and inflammatory stimuli. METHODS Human gastric epithelial cell lines (MKN7) were co-cultured with Campylobacter jejuni (C. jejuni). In order to investigate the effect of MUC1 expression on C. jejuni-induced cytokine production, MKN7 cells were transfected with 1:1 small interfering RNA (siRNA) to knock down the MUC1 gene using MUC1 targeting siRNA or non targeting siRNA as a control. The read out of the experiment was interleukin (IL)-8 concentration as a result of the inflammation process. This cytokine concentration was measured using ELISA and compared between the two groups. RESULTS This study demonstrated that by using siRNA transfection, knockdown of MUC1 expression in MKN7 human gastric epithelial cells suppressed IL-8 production at the early phase of incubation, but promoted an increase in IL-8 production at the late phase, in response to C. jejuni. CONCLUSION Knockdown of the MUC1 gene in MKN7 cells reduced IL-8 levels both in the cells with and without exposure to C. jejuni. This study provides direction for exploration of the intracelular mechanisms by which cell surface mucins modulates inflammation in the response of gastrointestinal epithelial cells to pathogens or other inflammatory stimuli.

Article Details

Issue

Vol. 31 No. 3 (2012)

Section

Review Article

The journal allows the authors to hold the copyright without restrictions and allow the authors to retain publishing rights without restrictions.

How to Cite

MUC1 modulates gastric epithelial immune response to bacteria or inflammatory stimuli. (2012). Universa Medicina, 31(3), 141-150. https://doi.org/10.18051/UnivMed.2012.v31.141-150

References

Linden SK, Sutton P, Karlsson NG, Korolik V, McGuckin MA. Mucins in the mucosal barrier to infection. Mucosal Immunol 2008;1:183-97.

Hattrup CL, Gendler SJ. Structure and function of the cell surface (tethered) mucins. Annu Rev Physiol 2008;70:431-57.

Kobayashi M, Lee H, Nakayama J, Fukuda, M. Roles of gastric mucin-type O-glycans in the pathogenesis of Helicobacter pylori infection. Glycobiology 2009;19:453-61.

McAuley JL, Linden SK, Ping CW, King RM, Pennington HL, Gendler SJ, et al. MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Invest 2007;117:2313-24.

McGuckin MA, Every AL, Skene CD, Linden SK, Chionh YT, Swierczak A, et al. MUC1 mucin limits both Helicobacter pylori

colonization of the murine gastric mucosa and associated gastritis. Gastroenterology 2007;133:1210-8.

Linden SK, Sheng YH, Every AL, Miles KM, Skoog EC, Florin TH, et al. MUC1 limits Helicobacter pylori infection both by steric

hindrance and by acting as a releasable decoy. PLoS Pathog 2009;5:e1000617.

Lu W, Hisatsune A, Koga T, Kato K, Kuwahara I, Lillehoj EP, et al. Cutting edge: enhanced pulmonary clearance of Pseudomonas aeruginosa by MUC1 knockout mice. J Immunol 2006;176:3890-4.

Ueno K, Koga T, Kato K, Golenbock DT, Gendler SJ, Kai H, et al. MUC1 mucin is a negative regulator of toll-like receptor signaling. Am J Respir Cell Mol Biol 2008;38:263-8.

Guang W, Ding H, Czinn SJ, Kim KC, Blanchard TG, Lillehoj EP. MUC1 cell surface mucin attenuates epithelial inflammation in

response to a common mucosal pathogen. J Biol Chem 2010;285:20547-57.

Lillehoj EP, Kim H, Chun EY, Kim KC. Pseudomonas aeruginosa stimulates phosphorylation of the airway epithelial

membrane glycoprotein MUC1 and activates MAP kinase. Am J Physiol Lung Cell Mol Physiol 2004;287:L809-15.

Thompson EJ, Shanmugam K, Hattrup CL, Kotlarczyk KL, Gutierrez A, Bradley JM, et al. Tyrosines in the MUC1 cytoplasmic tail modulate transcription via the extracellular

signal-regulated kinase 1/2 and nuclear factorkappa B pathways. Mol Cancer Res 2006;4:489-97.

Ahmad R, Raina D, Trivedi V, Ren J, Rajabi H, Kharbanda S, et al. MUC1 oncoprotein activates the I kappa B kinase beta complex and constitutive NF-kappa B signalling. Nat Cell Biol

;9:1419-27.

Hickey TE, McVeigh AL, Scott DA, Michielutti RE, Bixby A, Carroll SA, et al. Campylobacter jejuni cytolethal distending toxin mediates release of interleukin-8 from intestinal epithelial

cells. Infect Immun 2000;68:6535-41.

Zheng J, Meng J, Zhao S, Singh R, Song W. Campylobacter-induced interleukin-8 secretion in polarized human intestinal epithelial cells requires Campylobacter-secreted cytolethal

distending toxin- and Toll-like receptor-mediated activation of NF-kappa B. Infect Immun 2008;76:4498-508.

Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003;10:45-65.

Bradley JR. TNF-mediated inflammatory disease. J Pathol 2008;214:149-60.

Li Y, Dinwiddie DL, Harrod KS, Jiang Y, Kim KC. Anti-inflammatory effect of MUC1 during respiratory syncytial virus infection of lung epithelial cells in vitro. Am J Physiol Lung Cell Mol Physiol 2010;298:L558-63.