Immunomodulatory Response of the Middle Ear Epithelial Cells in Otitis Media.


Journal

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
ISSN: 1537-4505
Titre abrégé: Otol Neurotol
Pays: United States
ID NLM: 100961504

Informations de publication

Date de publication:
18 Jan 2024
Historique:
medline: 19 1 2024
pubmed: 19 1 2024
entrez: 19 1 2024
Statut: aheadofprint

Résumé

The middle ear (ME) epithelium transforms because of changed immunomodulation during infection. The epithelial cells of the tympanic cavity represent the first line of defense in the context of otitis media. They can convert from a typical mucosal site into a respiratory epithelium and vice versa. Our goal is to depict the specific immune response of epithelial cells after infection at the molecular level. The investigations were carried out on healthy and inflamed ME tissue, removed during surgical interventions in mouse and human models, and in a human in-vitro cell model in human ME epithelial cell line. We determined the epithelial localization of the protein expression of Toll- and NOD-like immune receptors and their associated signaling molecules using immunohistochemistry. In addition, we examined growth behavior and gene expression due to direct stimulation and inhibition. We found clinically and immunobiologically confirmed transformation of the inflamed ME epithelium depending on their origin, as well as differences in the distribution of Toll-like receptors and nucleotide-binding oligomerization domain-like receptors in the epithelial cell lining. Dysregulated gene and protein expression of the inflammatory and apoptotic genes could be modulated by stimulation and inhibition in the epithelial cells. The local ME mucosal tissue is believed to modulate downstream immune activity after pathogen invasion via intrinsic cellular mechanism. Using translation approaches to target these molecular pathways may offer more reliable clinical resolution of otitis media in the future.

Identifiants

pubmed: 38238924
doi: 10.1097/MAO.0000000000004096
pii: 00129492-990000000-00472
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024, Otology & Neurotology, Inc.

Déclaration de conflit d'intérêts

Conflict of interest: The authors declare that they have no other competing interests, commercial or financial relationships. Allen Ryan is a cofounder of Otonomy Inc., serves as a member of the Scientific Advisory Board, and holds an equity position in the company. The UCSD Committee on Conflict of Interest has approved this relationship. Otonomy, Inc., played no part in the research reported here.

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Auteurs

David Leffers (D)

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.

Zuzana Penxova (Z)

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.

Thorge Kempin (T)

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.

Markus Därr (M)

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.

Jonas Fleckner (J)

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.

Daniela Hollfelder (D)

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.

Allen F Ryan (AF)

Department of Surgery/Otolaryngology, University of California, San Diego, CA, USA.

Karl-Ludwig Bruchhage (KL)

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.

Arwa Kurabi (A)

Department of Surgery/Otolaryngology, University of California, San Diego, CA, USA.

Anke Leichtle (A)

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.

Classifications MeSH