Erica A Samuel1, Amy Burrows, Joseph E Kerschner. 1. Division of Pediatric Otolaryngology, Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, 9000 W. Wisconsin Avenue, Milwaukee, WI 53226, USA.
Abstract
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-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.
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-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.
Authors: T Chonmaitree; J A Patel; T Sim; R Garofalo; T Uchida; T Sim; V M Howie; M J Owen Journal: Ann Otol Rhinol Laryngol Date: 1996-12 Impact factor: 1.547
Authors: Joseph E Kerschner; Geza Erdos; Fen Ze Hu; Amy Burrows; Joseph Cioffi; Pawjai Khampang; Margaret Dahlgren; Jay Hayes; Randy Keefe; Benjamin Janto; J Christopher Post; Garth D Ehrlich Journal: Ann Otol Rhinol Laryngol Date: 2010-04 Impact factor: 1.547
Authors: Arwa Kurabi; Jasmine Lee; Chelsea Wong; Kwang Pak; Hal M Hoffman; Allen F Ryan; Stephen I Wasserman Journal: Innate Immun Date: 2014-03-20 Impact factor: 2.680
Authors: Joseph E Kerschner; Wenzhou Hong; Steven R Taylor; John A Kerschner; Pawjai Khampang; Kay C Wrege; Paula E North Journal: Int J Pediatr Otorhinolaryngol Date: 2012-11-30 Impact factor: 1.675
Authors: Joseph E Kerschner; Pawjai Khampang; Christy B Erbe; Alexander Kolker; Joseph A Cioffi Journal: Glycoconj J Date: 2009-12 Impact factor: 2.916
Authors: Joseph E Kerschner; Edward Horsey; Azad Ahmed; Christy Erbe; Pawjai Khampang; Joseph Cioffi; Fen Ze Hu; James Christopher Post; Garth D Ehrlich Journal: Arch Otolaryngol Head Neck Surg Date: 2009-01