Mucin Production and Mucous Cell Metaplasia in Otitis Media

Lin, Jizhen; Cayé‐Thomasen, Per; Tono, Tetsuya; Zhang, Quanan; Nakamura, Yoshihisa; Ling, Feng; Huang, Jianmin; Ye, Shengnan; Hu, Xiaohua; Kerschner, Joseph E.

doi:10.1155/2012/745325

Cited by 19 publications

(19 citation statements)

References 82 publications

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“…This observation has been confirmed by in situ hybridization, which shows clearly that MU-C5AC positive mucous cells are dominant in the Eustachian tube mucosa whereas MUC5B positive mucous cells are only in the mucous glands of the Eustachian tube and tracheal submucosal glands [12,13,31]. In the middle ear mucosa, few MUC5B messenger RNA (mRNA) transcripts are found in the biopsy specimens [29,32].…”

Section: Mucin Dysregulation In Middle Earmentioning

confidence: 71%

“…A total of 12 out of 20 mucins have been shown to be in the respiratory tract [12,13]. However, three to four mucins are identified from the middle ear mucosa; they are MUC5AC, MUC5B, MUC4, and MUC1.…”

Section: Mucin Dysregulation In Middle Earmentioning

confidence: 99%

“…Among them, MUC4 and MUC1 are basically membrane-bound mucins, not secretory ones, although they may appear in the middle ear effusion. Only MUC5B and MUC5AC are mucins found in COM [12,30]. It is known that MUC5B in humans responds to chronic stimuli [30,31].…”

Section: Mucin Dysregulation In Middle Earmentioning

confidence: 99%

“…Occasionally, MUC5AC may be upregulated in OM [30]. It is clear in the recent studies that MUC5B is the predominant one [12,13,29,30,32]. MUC5B is actually a mucin expressed in submucosal glands, instead of in the surface epithelia, but it is highly upregulated in COM [29,31,32].…”

Section: Mucin Dysregulation In Middle Earmentioning

confidence: 99%

“…Our recent findings indicate that specific mucins and mucin chaperones relevant to the mucociliary blanket are increased in OM with effusion [12,13]. On the other hand, other cytokines and mediators such as TNF-α and IFN-γ related to the cellular immunity of the middle ear are essential for the defense against middle ear infection.…”

mentioning

confidence: 91%

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Abnormal Innate and Adaptive Immunity in Otitis Media

Lin

2015

Otitis Media: State of the Art Concepts and Treatment

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Section: Mucin Dysregulation In Middle Earmentioning

confidence: 71%

Section: Mucin Dysregulation In Middle Earmentioning

confidence: 99%

Section: Mucin Dysregulation In Middle Earmentioning

confidence: 99%

Section: Mucin Dysregulation In Middle Earmentioning

confidence: 99%

mentioning

confidence: 91%

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Abnormal Innate and Adaptive Immunity in Otitis Media

Lin

2015

Otitis Media: State of the Art Concepts and Treatment

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Dexamethasone modulation ofMUC5ACandMUC2gene expression in a generalized model of middle ear inflammation

2015

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Objective To examine the effect of dexamethasone on basal and pro-inflammatory cytokines induced gel forming mucin expression in human middle ear epithelium culture (HMEEC-1). Methods HMEEC-1 was exposed to pro-inflammatory cytokines, TNF-α and IL-1β to identify optimal mucin induction. The HMEEC-1 was incubated with dexamethasone in the steady state and in the presence of pro-inflammatory cytokine stimulation. Expression of MUC2 and MUC5AC was determined by quantitative PCR. Results Pro-inflammatory cytokines, TNF-α and IL-1β, induced MUC2 and MUC5AC expression in HMEEC-1. Dexamethasone reduced steady state mRNA level of MUC5AC in a time (p<0.05) and dose dependent manner (p<0.0001). MUC2 was effectively suppressed at all time-points tested (p<0.05). Temporal difference between dexamethasone suppression of MUC2 and MUC5AC was demonstrated. Dexamethasone inhibits the pro-inflammatory cytokine induced expression of both MUC2 and MUC5AC. Conclusion This work provides a conclusive picture of the ability of using glucocorticoids to down-regulate mucin gene expression in human middle ear epithelium using a generalizable model of inflammation which is applicable to multiple potential causes of middle ear epithelium mucosal hypertrophy. This data adds to the promising potential of future interventions for patients with chronic otitis media.

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Analysis of Inflammatory Signaling in Human Middle Ear Cell Culture Models of Pediatric Otitis Media

et al. 2020

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Objectives/Hypothesis Cell culture models are valuable tools for investigation of the molecular pathogenesis of diseases including otitis media (OM). Previous study indicates that age‐, sex‐, and race‐associated differences in molecular signaling may impact disease pathophysiology. Currently, a singular immortalized middle ear epithelial (MEE) cell line exists, HMEEC‐1, derived from an adult without known middle ear disease. In this study, HMEEC‐1 and primary MEE cultures from pediatric patients with and without OM were stimulated with inflammatory cytokines or OM‐pathogenic bacterial lysates to examine differences in the response of molecules associated with OM pathogenesis. Study Design Case–control series. Methods MEE cultures were established from patients aged <6 years: two with recurrent OM (ROM), two with OM with effusion (OME), and one patient without OM who was undergoing cochlear implant surgery control undergoing cochlear implantation (Peds CI). Primary MEE cultures and HMEEC‐1 cells were stimulated with tumor necrosis factor‐α, interleukin (IL)‐1β, or nontypeable Haemophilus influenzae lysate. TNFA, IL1B, IL6, IL8, IL10, and MUC5B were assayed via quantitative polymerase chain reaction. IL‐8 was assayed by enzyme‐linked immunosorbent assay. Results Gene/protein target expressions were frequently higher in pediatric OM lines than in HMEEC‐1 and Peds CI. HMEEC‐1 cells were frequently less responsive to stimuli than all pediatric lines. OME lines were often more responsive than ROM lines. Conclusions OM may be associated with specific molecular phenotypes that are retained in primary cell culture. Adult‐derived HMEEC‐1 cells differ significantly in baseline expression and response of OM‐associated molecules relative to pediatric MEE cells. Work is underway to immortalize pediatric OM MEE cultures as improved tools for the OM research community. Level of Evidence 4 Laryngoscope, 131:410–416, 2021

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Mucin Production and Mucous Cell Metaplasia in Otitis Media

Cited by 19 publications

References 82 publications

Abnormal Innate and Adaptive Immunity in Otitis Media

Abnormal Innate and Adaptive Immunity in Otitis Media

Dexamethasone modulation ofMUC5ACandMUC2gene expression in a generalized model of middle ear inflammation

Analysis of Inflammatory Signaling in Human Middle Ear Cell Culture Models of Pediatric Otitis Media

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