Chinchilla middle ear epithelial mucin gene expression in response to inflammatory cytokines

Abstract

Objectives: To review the importance of mucin on a molecular level in the understanding of the pathophysiology of otitis media and to present new data demonstrating differential up-regulation of specific mucin genes during inflammation of middle ear epithelium.

Design: Primary chinchilla middle ear epithelial cultures (CMEECs) were established and exposed to tumor necrosis factor alpha and interleukin 1beta. Expression of chinchilla mucin genes 1, 2, 4, and 5AC was analyzed by means of reverse transcriptase-polymerase chain reaction after this exposure and compared with that of controls. Mucin secretion was also characterized by means of exclusion chromatography and liquid scintillation.

Results: The CMEECs exposed to interleukin 1beta and tumor necrosis factor alpha demonstrated significant up-regulation of mucin gene 2 (P = .005 and P = .007, respectively) and trends suggestive of up-regulation of mucin gene 5AC compared with the controls. These CMEECs also demonstrated significant increases in secretion of mucin compared with controls. Mucin genes 1 and 4 did not demonstrate up-regulation.

Conclusions: In CMEECs, the inflammatory mediators tumor necrosis factor alpha and interleukin 1beta cause a differential up-regulation and expression of mucin genes. Elucidating the effect of specific cytokines on the regulation of mucin secretion in the middle ear is vital to understanding the pathophysiology of otitis media. A greater understanding of these mechanisms and variations between individuals and pathogens has the potential to significantly alter the approach and management of otitis media in children and lead to novel therapeutic interventions.