Cytokine regulation of mucin secretion in a human middle ear epithelial model.
OBJECTIVE
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-1beta (IL-1beta), tumor necrosis factor-alpha (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-1beta 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-1beta and TNF-alpha demonstrated significant upregulation of mucin secretion in a dose-dependent fashion. Cultures exposed to IL-1beta at 100ng/ml and TNF-alpha at 200ng/ml showed increased mucin secretion in time-dependent experiments at 16h (P=0.00008) for TNF-alpha and 8 (P=0.028) and 16h (P=0.00001) for IL-1beta. IL-1ra and TNFab inhibited the effects of increased mucin secretion by IL-1beta and TNF-alpha.


CONCLUSIONS
IL-1beta 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.
Division of Pediatric Otolaryngology, Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, 9000 W. Wisconsin Avenue, Milwaukee, WI 53226, USA.
Erica A
EA
Samuel
Amy
A
Burrows
Joseph E
JE
Kerschner
D000906:Antibodies / Q000494:pharmacology; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004432:Ear, Middle / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D034381:Hearing Loss / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D009077:Mucins / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000906:Antibodies; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha