<i>MUC5AC</i>Expression in Human Middle Ear Epithelium of Patients With Otitis Media

Kerschner, Joseph E.; Tripathi, Shivani; Khampang, Pawjai; Papsin, Blake C.

doi:10.1001/archoto.2010.123

Cited by 31 publications

(27 citation statements)

References 10 publications

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“…Among these, MUC2 , MUC5AC , and MUC5B have been shown to play an important role in the pathogenesis of OM. 41–43 Abnormally high levels of mucin proteins have been demonstrated in middle ear effusions of CSOM patients. 44 This presence of mucin prevents the transmission of sound waves from the middle ear to the inner ear, hence leading to conductive hearing loss.…”

Section: Epithelial Cellsmentioning

confidence: 99%

Role of innate immunity in the pathogenesis of otitis media

Mittal

Kodiyan

Gerring

et al. 2014

International Journal of Infectious Diseases

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Summary Otitis media (OM) is a public health problem in both developed and developing countries. It is the leading cause of hearing loss and represents a significant healthcare burden. In some cases, acute OM progresses to chronic suppurative OM (CSOM), characterized by effusion and discharge, despite antimicrobial therapy. The emergence of antibiotic resistance and potential ototoxicity of antibiotics has created an urgent need to design non-conventional therapeutic strategies against OM based on modern insights into its pathophysiology. In this article, we review the role of innate immunity as it pertains to OM and discuss recent advances in understanding the role of innate immune cells in protecting the middle ear. We also discuss the mechanisms utilized by pathogens to subvert innate immunity and thereby overcome defensive responses. A better knowledge about bacterial virulence and host resistance promises to reveal novel targets to design effective treatment strategies against OM. The identification and characterization of small natural compounds that can boost innate immunity may provide new avenues for the treatment of OM. There is also a need to design novel methods for targeted delivery of these compounds into the middle ear, allowing higher therapeutic doses and minimizing systemic side effects.

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Section: Epithelial Cellsmentioning

confidence: 99%

Role of innate immunity in the pathogenesis of otitis media

Mittal

Kodiyan

Gerring

et al. 2014

International Journal of Infectious Diseases

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“…Otitis media is known to alter expression of selected cytokine [9], [11], mucin [12], tissue remodeling [11], and ion homeostasis genes [13] in the mouse middle ear (ME) and inner ear (IE). However, whole mouse genome studies of the gene expression in a setting of otitis media have not previously been undertaken.…”

Section: Introductionmentioning

confidence: 99%

Otitis Media Impacts Hundreds of Mouse Middle and Inner Ear Genes

et al. 2013

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ObjectiveOtitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.MethodsTo assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes.ResultsStatistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear.ConclusionWhole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media.

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“…Kerschner et al [411] have reported MUC5AC as fundamentally important in the development of ME mucoid effusions, hearing loss that also provides middle ear (ME) mucosal protection and bacterial clearance. This demonstrates MUC5AC gene changes in patients with otitis media (OM) and highlights the need for greater understanding of the molecular responses in OM; particularly that of mucin.…”

Section: Earmentioning

confidence: 99%

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

et al. 2015

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Mucins are major glycoprotein components of the mucus that coats the surfaces of cells lining the respiratory, digestive, gastrointestinal and urogenital tracts. They function to protect epithelial cells from infection, dehydration and physical or chemical injury, as well as to aid the passage of materials through a tract i.e., lubrication. They are also implicated in the pathogenesis of benign and malignant diseases of secretory epithelial cells. In Human there are two types of mucins, membrane-bound and secreted that are originated from mucous producing goblet cells localized in the epithelial cell layer or in mucous producing glands and encoded by MUC gene. Mucins belong to a heterogeneous family of high molecular weight proteins composed of a long peptidic chain with a large number of tandem repeats that form the so-called mucin domain. The molecular weight is generally high, ranging between 0.2 and 10 million Dalton and all mucins contain one or more domains which are highly glycosylated. The size and number of repeats vary between mucins and the genetic polymorphism represents number of repeats (VNTR polymorphisms), which means the size of individual mucins can differ substantially between individuals which can be used as markers. In human it is only MUC1 and MUC7 that have mucin domains with less than 40% serine and threonine which in turn could reduce number of PTS domains. Mucins can be considered as powerful two-edged sword, as its normal function protects from unwanted substances and organisms at an arm's length while, malfunction of mucus may be an important factor in human diseases. In this review we have unearthed the current status of different mucin proteins in understanding its role and function in various non-communicable diseases in human with special reference to its organ specific locations. The findings described in this review may be of direct relevance to the major research area in biomedicine with reference to mucin and mucin associated diseases.

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MUC5ACExpression in Human Middle Ear Epithelium of Patients With Otitis Media

Cited by 31 publications

References 10 publications

Role of innate immunity in the pathogenesis of otitis media

Role of innate immunity in the pathogenesis of otitis media

Otitis Media Impacts Hundreds of Mouse Middle and Inner Ear Genes

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

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