Genomic-based identification of novel potential biomarkers and molecular signaling networks in response to diesel exhaust particles in human middle ear epithelial cells Jee Young Kwon Moo Kyun Park Young Rok Seo Jae-Jun Song Email author Original Paper First Online: 10 May 2014 Received: 09 December 2013 Accepted: 24 March 2014 DOI :
10.1007/s13273-014-0012-0
Cite this article as: Kwon, J.Y., Park, M.K., Seo, Y.R. et al. Mol. Cell. Toxicol. (2014) 10: 95. doi:10.1007/s13273-014-0012-0
1
Citations
134
Downloads
Abstract Otitis media (OM) is the most common inflammatory disease of the middle ear cavity. Several factors including viral and bacterial infection, biofilm formation, congenital anomalies, and environmental factors have been recognized as the main causes of OM. Recent epidemiological studies showed that children living in areas with high concentrations of air pollutant including particulate matter and SO2 have significantly higher rates of OM compared with those in the control area. Another study reported that air pollutant exposure results in significant increases in pediatric OM. A large cohort study in Germany suggested that the prevalence of OM is related to air quality. Diesel exhaust particles (DEPs) are among the major toxic air pollutants of motor vehicle emissions. Hence, identifying the biomarkers of a signaling network for air pollutant (particularly DEPs)-mediated inflammatory responses would be meaningful. In this study, we identified novel biomarkers and potential molecular signaling networks induced by DEPs in human middle ear epithelial cells (HMEECs). Genomic expression analysis via microarray was used to discover novel biomarkers. A total of 254 genes were differentially expressed in DEPs-exposed HMEECs; 86 genes and 168 genes were up-and down-regulated, respectively. To verify reliable biomarkers and define meaningful signaling networks in the entire genome profiling, the in silico approach was applied. Based on genomic profiling analysis, we found several novel key molecular biomarkers, including SRC, MUC5AC, MUC2, MMP14, EIF1AK3, KITLG, NOD1 , and TP53 . Our findings suggested novel biomarkers for DEPs-responsive genes in HMEECs. Furthermore, we provided scientific evidence for the establishment of novel molecular signaling pathway associated with DEPs exposure in HMEECs.
Keywords Diesel exhaust particles Gene expression profile Human middle ear epithelial cells Molecular signaling network These authors contributed equally to this work.
References 1.
Heinrich, J. & Raghuyamshi, V. S. Air pollution and otitis media: a review of evidence from epidemiologic studies.
Curr Allergy AsthmrR
4 :302–309 (2004).
CrossRef Google Scholar 2.
Zemek, R., Szyszkowicz, M. & Rowe, B. H. Air pollution and emergency department visits for otitis media: a case-crossover study in Edmonton, Canada.
Environ Health Perspect
118 :1631–1636 (2010).
PubMedCentral PubMed CrossRef Google Scholar 3.
Riedl, M. & Diaz-Sanchez, D. Biology of diesel exhaust effects on respiratory function.
J Allergy Clin Immun
115 :221–228; quiz 229 (2005).
PubMed CrossRef Google Scholar 4.
Brauer, M.
et al. Traffic-related air pollution and otitis media.
Environ Health Perspect
114 :1414–1418 (2006).
PubMedCentral PubMed CrossRef Google Scholar 5.
Song, J. J.
et al. Effect of diesel exhaust particles on human middle ear epithelial cells.
Int J Pediatr Otorhi
76 :334–338 (2012).
CrossRef Google Scholar 6.
Wichmann, H. E. Diesel exhaust particles.
Inhal Toxicol
19 Suppl 1 :241–244 (2007).
Google Scholar 7.
Ghio, A. J., Smith, C. B. & Madden, M. C. Diesel exhaust particles and airway inflammation.
Curr Opin Pulm Med
18 :144–150 (2012).
PubMed CrossRef Google Scholar 8.
Jardim, M. J.
et al. Disruption of microRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways.
Environ Health Perspect
117 :1745–1751 (2009).
PubMedCentral PubMed Google Scholar 9.
Gottipolu, R. R.
et al. One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats.
Environ Health Perspect
117 :38–46 (2009).
PubMedCentral PubMed Google Scholar 10.
Yanagisawa, R.
et al. Complementary DNA microarray analysis in acute lung injury induced by lipopolysaccharide and diesel exhaust particles.
Exp Biol Med (Maywood)
229 :1081–1087 (2004).
Google Scholar 11.
Song, J. J.
et al. Effect of acrolein, a hazardous air pollutant in smoke, on human middle ear epithelial cells.
Int J Pediatr Otorhi
77 :1659–1664 (2013).
CrossRef Google Scholar 12.
Song, J. J., Kwon, J. Y., Park, M. K. & Seo, Y. R. Microarray analysis of gene expression alteration in human middle ear epithelial cells induced by micro particle.
Int J Pediatr Otorhi
77 :1760–1764 (2013).
CrossRef Google Scholar 13.
Cao, D., Bromberg, P. A. & Samet, J. M. Diesel particle-induced transcriptional expression of p21 involves activation of EGFR, Src, and Stat3.
Am J Resp Cell Mol
42 :88–95 (2010).
CrossRef Google Scholar 14.
Kerschner, J. E. Mucin gene expression in human middle ear epithelium.
The Laryngoscope
117 :1666–1676 (2007).
PubMed CrossRef Google Scholar 15.
Toribara, N. W.
et al. Human gastric mucin. Identification of a unique species by expression cloning.
J Biol Chem
268 :5879–5885 (1993).
PubMed Google Scholar 16.
Bobek, L. A., Tsai, H., Biesbrock, A. R. & Levine, M. J. Molecular cloning, sequence, and specificity of expression of the gene encoding the low molecular weight human salivary mucin (MUC7).
J Biol Chem
268 :20563–20569 (1993).
PubMed Google Scholar 17.
Shankar, V., Gilmore, M. S., Elkins, R. C. & Sachdev, G. P. A novel human airway mucin cDNA encodes a protein with unique tandem-repeat organization.
The Biochem J
300(Pt 2) :295–298 (1994).
Google Scholar 18.
Williams, S. J.
et al. Muc13, a novel human cell surface mucin expressed by epithelial and hemopoietic cells.
J Biol Chem
276 :18327–18336 (2001).
PubMed CrossRef Google Scholar 19.
Pallesen, L. T.
et al. Isolation and characterization of MUC15, a novel cell membrane-associated mucin.
Eur J Biochem / FEBS
269 :2755–2763 (2002).
CrossRef Google Scholar 20.
Gum, J. R., Jr.
et al. MUC17, a novel membrane-tethered mucin.
Biochem Bioph Res Co
291 :466–475 (2002).
CrossRef Google Scholar 21.
Higuchi, T.
et al. Molecular cloning, genomic structure, and expression analysis of MUC20, a novel mucin protein, up-regulated in injured kidney.
J Biol Chem
279 :1968–1979 (2004).
PubMed CrossRef Google Scholar 22.
Kerschner, J. E., Meyer, T. K. & Burrows, A. Chinchilla middle ear epithelial mucin gene expression in response to inflammatory cytokines.
Arch Otolaryngol Head Neck Surg
130 :1163–1167 (2004).
PubMed CrossRef Google Scholar 23.
Diamond, G., Legarda, D. & Ryan, L. K. The innate immune response of the respiratory epithelium.
Immunol Rev
173 :27–38 (2000).
PubMed CrossRef Google Scholar 24.
Ubell, M. L., Khampang, P. & Kerschner, J. E. Mucin gene polymorphisms in otitis media patients.
The Laryngoscope
120 :132–138 (2010).
PubMedCentral PubMed CrossRef Google Scholar 25.
Ubell, M. L., Kerschner, J. E., Wackym, P. A. & Burrows, A. MUC2 expression in human middle ear epithelium of patients with otitis media.
Arch Otolaryngol Head Neck Surg
134 :39–44 (2008).
PubMedCentral PubMed CrossRef Google Scholar 26.
Kerschner, J. E., Tripathi, S., Khampang, P. & Papsin, B. C. MUC5AC expression in human middle ear epithelium of patients with otitis media.
Arch Otolaryngol Head Neck Surg
136 :819–824 (2010).
PubMedCentral PubMed CrossRef Google Scholar 27.
Cho, J. G.
et al. Effects of cigarette smoking on mucin production in human middle ear epithelial cells.
Int J Pediatr Otorhi
73 :1447–1451 (2009).
CrossRef Google Scholar 28.
Kim, M. G.
et al. TLR-9, NOD-1, NOD-2, RIG-I and immunoglobulins in recurrent otitis media with effusion.
Int J Pediatr Otorhi
74 :1425–1429 (2010).
CrossRef Google Scholar 29.
Bayram, H.
et al. Effect of serum on diesel exhaust particles (DEP)-induced apoptosis of airway epithelial cells in vitro.
Toxicol Lett
218 :215–223 (2013).
PubMed CrossRef Google Scholar © The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht 2014
Authors and Affiliations Jee Young Kwon Moo Kyun Park Young Rok Seo Jae-Jun Song Email author 1. Department of Life Science, Institute of Environmental Medicine Dongguk University Seoul Korea 2. Department of Otorhinolaryngology-Head and Neck Surgery Seoul National University College of Medicine Seoul Korea 3. Department of Otorhinolaryngology-Head and Neck Surgery Korea University College of Medicine Seoul Korea