Participation of Ras and extracellular regulated kinase in the hyperplastic response of middle-ear mucosa during bacterial otitis media
2002 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, Vol. 186, no 12, 1761-9 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2002. Vol. 186, no 12, 1761-9 p.
Animals, Butadienes/pharmacology, Disease Models; Animal, Ear; Middle/metabolism/*pathology, Enzyme Inhibitors/pharmacology, Haemophilus Infections/*pathology, Haemophilus influenzae, Hyperplasia, In Vitro, Male, Methionine/*analogs & derivatives/pharmacology, Mitogen-Activated Protein Kinases/analysis/*physiology, Mucous Membrane/metabolism/pathology, Nitriles/pharmacology, Otitis Media/*pathology, Rats, Research Support; U.S. Gov't; Non-P.H.S., Research Support; U.S. Gov't; P.H.S., Signal Transduction/drug effects, Time Factors, ras Proteins/analysis/*physiology
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-83401DOI: 10.1086/345798PubMedID: 12447762OAI: oai:DiVA.org:uu-83401DiVA: diva2:111309