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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

Keyword

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

MEDICINE

MEDICIN

Publication and Content Type

ref (subject category)

art (subject category)