Participation of Ras and extracellular regulated kinase in the hyperplastic response of middle-ear mucosa during bacterial otitis media.
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.
Palacios
Sean D
SD
Department of Head and Neck Surgery, University of California, San Diego, School of Medicine, La Jolla, California, USA.
Pak
Kwang
K
Kayali
Ayse G
AG
Rivkin
Alexander Z
AZ
Aletsee
Christoph
C
Melhus
Asa
A
Webster
Nicholas J G
NJ
Ryan
Allen F
AF
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*
D002070:Butadienes; D004791:Enzyme Inhibitors; C096856:FTI 277; D009570:Nitriles; C113580:U 0126; D008715:Methionine; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins