Anke Leichtle1, David Leffers1, Markus Georg Daerr1, Clara Draf2, Arwa Kurabi2, Allen F Ryan2, Jan Rupp3, Karl-Ludwig Bruchhage1. 1. Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Universitätsklinikum Schleswig-Holstein Campus - Lübeck HNO Klinik, Lübeck, Germany. 2. Department of Surgery/ Otolaryngology, University of California San Diego, La Jolla, United States. 3. Klinik für Infektiologie und Mikrobiologie, Universitätsklinikum Schleswig-Holstein - Campus Lübeck, Lübeck, Germany.
Abstract
INTRODUCTION: The etiopathogenesis of chronic otitis media epitympanalis/cholesteatoma and its proliferative destructive course with possible complications such as destruction of bony structures with hearing loss, vestibular dysfunction, facial nerve paralysis and intracranial complications are still unexplained. Surgery is still the way to go. New studies are increasingly looking at the innate immune system. METHODS: Our studies were carried out in a mouse model in WT mice and immundeficient KO-mice, as well as in cholesteatoma and healthy ear canal skin and middle ear tissue, which was removed during ear surgery. The expression analyses were carried out at the gene and protein level using TNF as the major target for therapy evaluation. By means of TUNEL staining and immunohistochemistry the level of apoptosis was evaluated. RESULTS: The uncontrolled undirected cholesteatoma growth shows an immunomodulatory profile with up and down-regulation of various gene networks, especially those involved in TNF downstream and upstream signaling pathways. TNF in cholesteatoma is modulated both inflammatorily and apoptotically and therefore is suitable as a possible therapeutic approach in various models. CONCLUSIONS: Cholesteatoma might be immunomodulatory regulated. Thieme. All rights reserved.
INTRODUCTION: The etiopathogenesis of chronic otitis media epitympanalis/cholesteatoma and its proliferative destructive course with possible complications such as destruction of bony structures with hearing loss, vestibular dysfunction, facial nerve paralysis and intracranial complications are still unexplained. Surgery is still the way to go. New studies are increasingly looking at the innate immune system. METHODS: Our studies were carried out in a mouse model in WT mice and immundeficient KO-mice, as well as in cholesteatoma and healthy ear canal skin and middle ear tissue, which was removed during ear surgery. The expression analyses were carried out at the gene and protein level using TNF as the major target for therapy evaluation. By means of TUNEL staining and immunohistochemistry the level of apoptosis was evaluated. RESULTS: The uncontrolled undirected cholesteatoma growth shows an immunomodulatory profile with up and down-regulation of various gene networks, especially those involved in TNF downstream and upstream signaling pathways. TNF in cholesteatoma is modulated both inflammatorily and apoptotically and therefore is suitable as a possible therapeutic approach in various models. CONCLUSIONS: Cholesteatoma might be immunomodulatory regulated. Thieme. All rights reserved.
Authors: Anke Leichtle; Arwa Kurabi; David Leffers; Markus Därr; Clara Sophia Draf; Allen Frederic Ryan; Karl-Ludwig Bruchhage Journal: Front Cell Infect Microbiol Date: 2022-03-30 Impact factor: 5.293