title: In vitro study of IL-8 and goblet cells: possible role of IL-8 in the aetiology of otitis media with effusion.
abstract: One of the main characteristics of otitis media with effusion (OME) is the differentiation of basal cells into goblet cells with subsequent proliferation in a modified respiratory epithelium leading to the formation of mucin-rich effusion in the middle ear cleft. In order to determine the effect of pro-inflammatory cytokines identified in OME, e.g. IL-1beta, tumour necrosis factor (TNF)-alpha, IL-6 and IL-8, on goblet cells, and to clarify the role of IL-8 in particular, we used the human goblet cell line HT29-MTX, which secretes two OME-related mucins: MUC5AC and MUC5B. IL-1beta and TNF-alpha stimulated the secretion of IL-8 in HT29-MTX goblet cells. Dose- (2-200 ng/ml) and time- (0-5 days) response studies of IL-8-induced mucin secretion were carried out. IL-8 upregulated the secretion of MUC5AC and MUC5B mucins in a concentration-dependent manner, with a maximum response at an IL-8 concentration of 20 ng/ml. IL-8 (20 ng/ml)-mediated mucin secretion persisted for up to 5 days, with a peak response 72 h after the addition of cytokine. These results suggest that: (i) goblet cells are target cells for the pro-inflammatory cytokines IL-1beta, TNF-alpha and IL-8 and can contribute to the pathogenesis of OME by increasing both the concentration of IL-8 and the secretion of mucin; and (ii) IL-8 stimulates prolonged mucin secretion from goblet cells and may be involved in the maintenance of the disease in the chronic stage.
authors.affiliation: Department of Physiological Sciences, Medical School, University of Newcastle, Newcastle upon Tyne, UK. Marina.Smirnova@ncl.ac.uk
authors.forename: Marina G
authors.initials: MG
authors.lastname: Smirnova
authors.forename: John P
authors.initials: JP
authors.lastname: Birchall
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Pearson
mesh_terms: D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology; D004432:Ear, Middle / Q000166:cytology; D020397:Goblet Cells / Q000166:cytology / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology / Q000502:physiology; D016209:Interleukin-8 / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism; D010034:Otitis Media with Effusion / Q000209:etiology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016209:Interleukin-8; D009077:Mucins