The role of Fas-mediated apoptosis in otitis media: Observations in the lpr/lpr mouse

Rivkin, Alexander; Palacios, Sean D.; Pak, Kwang; Bennett, Thecla; Ryan, Allen F.

doi:10.1016/j.heares.2005.04.010

Cited by 14 publications

(9 citation statements)

References 21 publications

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“…This indicates that mast cells are an important component of the innate immune response of the ME cavity during the initial stages of OM. Rivkin et al (2005) found that mucosal hyperplasia during OM was enhanced in lpr/lpr mice when compared to wild-type controls. In addition, the recovery of the mucosa was significantly delayed in Fas-deficient mice.…”

Section: Host Genetic Factors Underlying Otitis Mediamentioning

confidence: 85%

Mouse models for human otitis media

Trune

Zheng

2009

Brain Research

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Otitis media (OM) remains the most common childhood disease and its annual costs exceed $5 billion. Its potential for permanent hearing impairment also emphasizes the need to better understand and manage this disease. The pathogenesis of OM is multifactorial and includes infectious pathogens, anatomy, immunologic status, genetic predisposition, and environment. Recent progress in mouse model development is helping to elucidate the respective roles of these factors and to significantly contribute toward efforts of OM prevention and control. Genetic predisposition is recognized as an important factor in OM and increasing numbers of mouse models are helping to uncover the potential genetic bases for human OM. Furthermore, the completion of the mouse genome sequence has offered a powerful set of tools for investigating gene function and is generating a rich resource of mouse mutants for studying the genetic factors underlying OM.

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Section: Host Genetic Factors Underlying Otitis Mediamentioning

confidence: 85%

Mouse models for human otitis media

Trune

Zheng

2009

Brain Research

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ E-liquids induced apoptosis and autophagy signaling in HMEECs. The previous studies suggested that apoptosis and autophagy induction are the critical response of middle ear epithelium during OM 22,23 . To investigate the mechanism of cell death when the cells were exposed to e-liquids, we first analyzed apoptosis signaling by flow cytometry analysis.…”

Section: E-liquids Caused Dysregulation Of Water Channels In Hmeecs mentioning

confidence: 99%

Comparison between in vitro toxicities of tobacco- and menthol-flavored electronic cigarette liquids on human middle ear epithelial cells

Mun

Chae

et al. 2020

Sci Rep

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Since electronic-cigarettes (e-cigarettes) are considered less toxic than conventional tobacco smoking, the use of e-cigarettes has increased, and the market for e-cigarette liquids (e-liquids) is continuously increasing. However, many studies showed that e-cigarettes may cause various harmful effects in lung, oral and heart. In this study, we investigated the effects of e-liquids on otitis media (OM) using human middle ear epithelial cells (HMEECs). Menthol-flavored e-liquid induced significant cell death in HMEECs (IC 50 : 1.45 ± 0.14%) and tobacco-flavored e-liquid led to increase in inflammatory cytokine levels and higher mucin production. Flavored e-liquids decreased the mRNA levels of genes encoding epithelial sodium channels (ENaCs) in HMEECs. Apoptosis and autophagy reactions were induced by exposure of HMEECs to menthol-and tobacco-flavored e-liquids. Tobacco-flavored e-liquids caused a greater increase in the levels of autophagosome marker, LC3-II, compared to menthol-flavored e-liquids, which was followed by cell death. These results demonstrate that flavored e-liquids cause cytotoxicity via apoptosis, autophagy, inflammatory response, and mucin production in HMEECs. The flavors present in e-liquids might be a risk factor for the development of otitis media. Otitis media (OM) is an ear infectious disease and its symptoms include pain, inflammation, and flow of fluid out of the middle ear cavity. Particularly, almost 50% of children experience OM under the age of 3 years 1. The middle ear infection usually presents as acute otitis media (AOM) within one week, but can develop into chronic otitis media (COM). COM persists over 2 weeks, and can cause serious inflammation in the inner ear and hearing loss. OM is typically induced by bacterial and viral infection in the middle ear during the dysfunction of the eustachian tube and nasal cavity 2. However, recent studies have investigated the relationship between environmental factors (smoke, diesel particles, urban particles, and Asian sand dust) and OM incidence 3-6. Electronic cigarettes (e-cigarettes) are available on the market as an alternative to conventional tobacco smoking. E-cigarettes were introduced to help reduce smoking habit by providing nicotine selectively from 0 to 36 mg/ mL 7 in various flavors of e-cigarette liquids (e-liquids). Many users consider e-cigarettes to be safer than tobacco cigarettes, which led to increase in marketing of e-cigarettes for nicotine delivery. However, several animal and human cohort studies have been conducted since 2014 related to the harmful effects of e-cigarettes on human health, including increased tumorigenicity in lung and bladder 8 , cardiovascular system 9 , and alterations in the oral and gut microbiota in humans 10. E-cigarettes vaporize flavor and nicotine-containing fluids through a heating coil in an atomizer, and the user inhales the aerosol. Although e-liquids do not contain harmful agents, such as tar, benzene, carbon monoxide, and formaldehyde, their safety concerns have been raised, except for ...

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“…The deaf mouse mutant Jeff (Jf) which exhibits chronic proliferative OM and the OM-susceptible Junbo mice (Parkinson et al, 2006) are two of the few mouse models available for OM studies. Pathogen-induced OM models have been extensively studied (Bikhazi and Ryan, 1995;Ebmeyer et al, 2005;Melhus and Ryan, 2003;Rivkin et al, 2005;Ryan et al, 1989), but the study of mutant mice has revealed genes that are difficult to identify in wild-type mice Parkinson et al, 2006). Our strategy is to compare many strains of inbred mice to identify genes that are differentially expressed in those mice with a predisposition toward OM or deafness.…”

Section: Introductionmentioning

confidence: 99%

Tympanometry assessment of 61 inbred strains of mice

et al. 2007

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Otitis media (OM) accounts for more than 20 million clinic visits in the United States every year. Resistance to antibiotics has hampered current management of the disease. Identification of genetic factors underlying susceptibility to OM is greatly needed in order to develop alternative treatment strategies. Genetically defined inbred mouse strains offer a powerful tool for dissecting genetic and environmental factors that may lead to OM in mice. Here, we report a study of middle ear function of 61 genetically diverse inbred strains of mice using tympanometry. Of the 61 inbred strains tested, the 129P1/ReJ, 129P3/J, 129S1/SvImJ, 129X1/SvJ, A/HeJ, BALB/cJ, BUB/BnJ, C57L/J, EL/SuzSeyFrkJ, FVB/NJ, I/LnJ, LP/J, NZB/BlNJ, PL/J and YBR/Ei strains exhibited tympanograms that were statistically different from other healthy strains according to parameters including middle ear pressure, volume and compliance. These differences are most likely the result of genetic factors that, when understood, will facilitate prevention and treatment of otitis media in humans. In addition, a negative correlation between age and compliance of the tympanic membrane was discovered. This is the first report to successfully use tympanometry to measure mouse middle ear function, which has been a challenge for the hearing research field because of the mouse's tiny ear size.

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The role of Fas-mediated apoptosis in otitis media: Observations in the lpr/lpr mouse

Cited by 14 publications

References 21 publications

Mouse models for human otitis media

Mouse models for human otitis media

Comparison between in vitro toxicities of tobacco- and menthol-flavored electronic cigarette liquids on human middle ear epithelial cells

Tympanometry assessment of 61 inbred strains of mice

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