Activation of the Transforming Growth Factor Beta Pathway in Bacterial Otitis Media

Objectives: Granulation tissue is common in otitis media (OM), yet little is known about the signaling pathways in the formation of granulation tissue in response to infections. En this study, we sought to investigate the activation of the transforming growth factor beta (TGF-beta) signaling pathway in the formation of granulation tissue in response to middle ear pathogens. Methods: Rat OM models were made by inoculating pneumococcus type 6A or nontypeable Haemophilus influenzae into the middle ear cavity or by obstructing the eustachian tube. Various pathway activities in the middle ear mucosa were analyzed with microarrays. Results: The TGF-beta signaling pathway was highly regulated in the middle ear cleft with bacterial OM, but not in the ears with eustachian tube obstruction. In ears with bacterial OM, the TGF-beta signaling pathway products were higher in Haemophilus-infected ears than in pneumococcus-infected ears. Conclusions: Bacterial OM triggers granulation tissue to thrive in the middle ear cleft of rats. Nontypeable H influenzae is more potent than pneumococcus type 6A in the formation of granulation tissue. Eustachian tube obstruction alone did not contribute to granulation tissue formation in the middle ear.