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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-1 g , tumour necrosis factor (TNF)- f , 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-1 g and TNF- f 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-1 g , TNF- f 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.