Cytokine regulation of mucin secretion in a human middle ear epithelial model

Objectives: Middle ear mucins are associated with otitis media (OM), contribute to hearing loss and are regulated by cytokines. This work investigates the regulation of mucin secretion from human middle ear epithelial cells (HMEEC) by inflammatory cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor-a (TNF-alpha) and cytokine inhibitors interleukin-1 receptor antagonist (IL-1ra) and anti-tumor necrosis factor-alpha antibody (TNFab). Methods: HMEEC were exposed to IL-1 beta and TNF-alpha in a dose- and time-dependent manner. Cytokine stimulated HMEEC were also exposed to IL-1ra and TNFab in a dose-dependent manner. Mucin secretion was characterized by exclusion chromatography and liquid scintillation. Results: HMEEC exposed to IL-1 beta and TNF-alpha demonstrated significant upregulation of mucin secretion in a dose-dependent fashion. Cultures exposed to IL-1 beta at 100 ng/ml and TNF-alpha at 200 ng/ml showed increased mucin secretion in time-dependent experiments at 16 h (P = 0.00008) for TNF-alpha and 8 (P = 0.028) and 16 h (P = 0.00001) for IL-1 beta. IL-1ra and TNFab inhibited the effects of increased mucin secretion by IL-1 beta and TNF-alpha. Conclusions: IL-1 beta and TNF-alpha upregulate mucin secretion from HMEEC in a dose- and time-dependant manner and these effects can be inhibited by cytokine blockade. Improved understanding of these mechanisms has the potential to alter the approach and management of OM and lead to novel therapeutic interventions. (c) 2007 Elsevier Ltd. All rights reserved.