Ultrastructural Pathology of the Middle Ear Mucosa in Serous Otitis Media

Lim, David J.; Birck, Herbert G.

doi:10.1177/000348947108000611

Cited by 138 publications

(63 citation statements)

References 25 publications

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“…Mucosal hyperplasia is a major feature of OM (17) and can contribute to its symptoms and to irreversible ME disease (32,36). It is therefore of interest to determine how mucosal hyperplasia is regulated in the ME.…”

Section: Discussionmentioning

confidence: 99%

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Jun N-Terminal Protein Kinase Enhances Middle Ear Mucosal Proliferation during Bacterial Otitis Media

Furukawa

Ebmeyer

Pak³

et al. 2007

Infect Immun

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Mucosal hyperplasia is a characteristic component of otitis media. The present study investigated the participation of signaling via the Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase in middle ear mucosal hyperplasia in animal models of bacterial otitis media. Otitis media was induced by the inoculation of nontypeable Haemophilus influenzae into the middle ear cavity. Western blotting revealed that phosphorylation of JNK isoforms in the middle ear mucosa preceded but paralleled mucosal hyperplasia in this in vivo rat model. Nuclear JNK phosphorylation was observed in many cells of both the mucosal epithelium and stroma by immunohistochemistry. In an in vitro model of primary rat middle ear mucosal explants, bacterially induced mucosal growth was blocked by the Rac/Cdc42 inhibitor Clostridium difficile toxin B, the mixed-lineage kinase inhibitor CEP11004, and the JNK inhibitor SP600125. Finally, the JNK inhibitor SP600125 significantly inhibited mucosal hyperplasia during in vivo bacterial otitis media in guinea pigs. Inhibition of JNK in vivo resulted in a diminished proliferative response, as shown by a local decrease in proliferating cell nuclear antigen protein expression by immunohistochemistry. We conclude that activation of JNK is a critical pathway for bacterially induced mucosal hyperplasia during otitis media, influencing tissue proliferation.

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Section: Discussionmentioning

confidence: 99%

“…Hyperplasia of the ME mucosa is an important component of OM, involving substantial cell proliferation and differentiation (17). Hyperplasia contributes to the deleterious sequelae of OM, including the production of mucous secretions of ME effusions (36).…”

mentioning

confidence: 99%

Jun N-Terminal Protein Kinase Enhances Middle Ear Mucosal Proliferation during Bacterial Otitis Media

Furukawa

Ebmeyer

Pak³

et al. 2007

Infect Immun

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“…This minimal mucosa ranges from 15 to 20 m thick. During otitis media the middle ear mucosa has the unique capacity to grow and proliferate to many times its original thickness, into a highly structured, pseudostratified, columnar epithelial complex (23,25,33,42). Hyperplasia of the mucosa is associated with many of the negative sequelae of middle ear infection.…”

mentioning

confidence: 99%

“…Hyperplasia of the mucosa is associated with many of the negative sequelae of middle ear infection. Production of mucus and other elements of middle ear effusions is closely linked to the production of additional mucosal cells and their transformation into a secretory phenotype (33,51 …”

mentioning

confidence: 99%

Role of p38 Mitogen-Activated Protein Kinase in Middle Ear Mucosa Hyperplasia during Bacterial Otitis Media

Palacios¹,

Pak

Rivkin³

et al. 2004

Infect Immun

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Hyperplasia of the middle ear mucosa contributes to the sequelae of acute otitis media. Understanding the signal transduction pathways that mediate hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Endotoxin derived from bacteria involved in middle ear infection can contribute to the hyperplastic response. The p38 mitogen-activated protein kinase (MAPK) is known to be activated by endotoxin as well as cytokines and other inflammatory mediators that have been documented in otitis media. We assessed the activation of p38 in the middle ear mucosa of an in vivo rat bacterial otitis media model. Strong activity of p38 was observed 1 to 6 h after bacterial inoculation. Activity continued at a lower level for at least 7 days. The effects of p38 activation were assessed using an in vitro model of rat middle ear mucosal hyperplasia in which mucosal growth is stimulated by nontypeable Haemophilus influenzae during acute otitis media. Hyperplastic mucosal explants treated with the p38␣ and p38␤ inhibitor SB203580 demonstrated significant inhibition of otitis media-stimulated mucosal growth. The results of this study suggest that intracellular signaling via p38 MAPK influences the hyperplastic response of the middle ear mucosa during bacterial otitis media.Pathologic conditions related to otitis media include middle ear effusion, adhesive otitis, tympanic membrane perforation, tympanosclerosis, scarring of the middle ear mucosa, cholesteatoma, and atelectasis (4,24,37,38,43,46). These sequelae can lead to permanent damage of the middle ear cavity, resulting in hearing loss or impairment (1). A contributing factor to such morbidity during otitis media is the transformation of the inflamed middle ear mucosa. Normally, the middle ear mucosa consists of a simple squamous epithelium overlying a thin lamina propria that adheres to the underlying periosteum (21). This minimal mucosa ranges from 15 to 20 m thick. During otitis media the middle ear mucosa has the unique capacity to grow and proliferate to many times its original thickness, into a highly structured, pseudostratified, columnar epithelial complex (23,25,33,42). Hyperplasia of the mucosa is associated with many of the negative sequelae of middle ear infection. Production of mucus and other elements of middle ear effusions is closely linked to the production of additional mucosal cells and their transformation into a secretory phenotype (33,51

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“…Therefore, the bolus of mucus containing pathogenic bacteria may enter into the tympanic cavity when the tube attempts to open. The proportion of the ciliated and secretory cells reflects the history of inflammation in the middle ear, suggesting the middle ear epithelial cell type is in dynamic state [12]. The epithelial cells are also known to elaborate antimicrobial molecules, which constitute the innate immune defense mechanism [3].…”

Section: Middle Ear Epitheliummentioning

confidence: 99%

Establishment of Cell Lines from the Human Middle and Inner Ear Epithelial Cells

Lim

Moon

2011

Advances in Experimental Medicine and Biology

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Ultrastructural Pathology of the Middle Ear Mucosa in Serous Otitis Media

Cited by 138 publications

References 25 publications

Jun N-Terminal Protein Kinase Enhances Middle Ear Mucosal Proliferation during Bacterial Otitis Media

Jun N-Terminal Protein Kinase Enhances Middle Ear Mucosal Proliferation during Bacterial Otitis Media

Role of p38 Mitogen-Activated Protein Kinase in Middle Ear Mucosa Hyperplasia during Bacterial Otitis Media

Establishment of Cell Lines from the Human Middle and Inner Ear Epithelial Cells

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