title: Participation of Ras and extracellular regulated kinase in the hyperplastic response of middle-ear mucosa during bacterial otitis media.
abstract: Hyperplasia of middle-ear mucosa (MEM) during otitis media (OM) is thought to be partially mediated by the actions of growth factors and their receptors. The intracellular pathway leading from the small G-protein Ras to the extracellular regulated kinases (Erks) often links growth factor stimulation to cellular proliferation. This study assessed whether this pathway is involved in MEM hyperplasia during bacterial OM via the activation of Erk1/Erk2 in MEM of an in vivo rat bacterial OM model. Activation was maximal at 1 and 6 h and at 1 week after introduction of bacteria into the middle ear. Additionally, an in vitro model of rat MEM in bacterial OM was treated with farnesyl transferase inhibitor 277 or the Mek inhibitor U0126. MEM explants treated with either inhibitor demonstrated significant suppression of bacterially induced growth. These data support a role for Ras and Erk signaling in MEM hyperplasia during bacterial OM.
authors.affiliation: Department of Head and Neck Surgery, University of California, San Diego, School of Medicine, La Jolla, California, USA.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Palacios
authors.forename: Kwang
authors.initials: K
authors.lastname: Pak
authors.forename: Ayse G
authors.initials: AG
authors.lastname: Kayali
authors.forename: Alexander Z
authors.initials: AZ
authors.lastname: Rivkin
authors.forename: Christoph
authors.initials: C
authors.lastname: Aletsee
authors.forename: Asa
authors.initials: A
authors.lastname: Melhus
authors.forename: Nicholas J G
authors.initials: NJ
authors.lastname: Webster
authors.forename: Allen F
authors.initials: AF
authors.lastname: Ryan
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000378:metabolism / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006192:Haemophilus Infections / Q000473:pathology*; D006193:Haemophilus influenzae; D006965:Hyperplasia; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000502:physiology*; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D010033:Otitis Media / Q000473:pathology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D018631:ras Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; C096856:FTI 277; D009570:Nitriles; C113580:U 0126; D008715:Methionine; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins