title: Induction of mucous cell metaplasia by tumor necrosis factor alpha in rat middle ear: the pathological basis for mucin hyperproduction in mucoid otitis media.
abstract: Mucoid otitis media (MOM), one of the leading causes of acquired hearing loss in children, is characterized by mucous cell hyperplasia in the middle ear cleft associated with mucin accumulation in the middle ear cavity. The factors that stimulate mucous cell metaplasia-hyperplasia and mucin hyperproduction are poorly understood. Recent studies demonstrated that tumor necrosis factor alpha (TNF-alpha), present in human middle ear effusion, stimulated mucin production in vitro and up-regulated mucin gene expression in vivo. These findings suggest that TNF-alpha is important in the development of mucous cell metaplasia-hyperplasia. This study demonstrated that inoculation of TNF-alpha into the middle ear cavity followed by eustachian tube obstruction stimulated mucous cell metaplasia-hyperplasia in the middle ear cleft, accompanied by abundant mucin or mucin-like glycoproteins in the middle ear effusion--a phenotype of MOM in humans. This finding suggests that TNF-alpha plays a key role in the pathogenesis of MOM through induction of mucous cell metaplasia-hyperplasia and mucin production.
authors.affiliation: University of Minnesota Otitis Media Research Center, Department of Otolaryngology, University of Minnesota School of Medicine, Minneapolis, USA.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kawano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Haruta
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Youngki
authors.initials: Y
authors.lastname: Kim
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Schachern
authors.forename: Michael M
authors.initials: MM
authors.lastname: Paparella
authors.forename: Jizhen
authors.initials: J
authors.lastname: Lin
mesh_terms: D000818:Animals; D004432:Ear, Middle / Q000473:pathology*; D005064:Eustachian Tube; D006801:Humans; D006965:Hyperplasia; D008679:Metaplasia; D008854:Microscopy, Electron; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010034:Otitis Media with Effusion / Q000209:etiology* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D009077:Mucins; D014409:Tumor Necrosis Factor-alpha