Goblet cells are the main mucus-producing cell type within the airway epithelium and goblet cell hyperplasia is a common pathology

of asthma [7]. IL-13 has been implicated as a key pathogenic cytokine in allergic asthma and Kondo and colleagues have suggested that it contributes to the differentiation of ciliated cells into goblet cells in asthmatic epithelium [8] and [9]. In addition it has been previously reported that both paediatric and adult epithelium exposed to IL-13 expressed increased goblet cell number and levels of MUC5AC, the major mucus forming mucin, in both healthy and asthmatic epithelium [10], [11], [12], [13] and [14]. IL-13 has been studied in detail using a number of Venetoclax solubility dmso different models in an attempt to re-create the asthmatic phenotype. Early

studies included experiments using mice sensitised with ovalbumin, which then receive see more a further allergic ‘hit’ resulting in an increase in MUC5AC expression and goblet cell number [15] and [16]. The effects of IL-13 have also been assessed using in vitro adult normal human bronchial epithelial cell cultures and it has been shown to increase goblet cell density by ten times as well as increasing MUC5AC expression, indicating a central role for IL-13 in allergic asthma [17]. IL-31 is produced by activated CD4+ T cells, mainly from the Th2 subset [6] and may work synergistically with IL-13 to modulate bronchial epithelial cell function. IL-31 over-expression has been well documented as having pathogenic effects in atopic dermatitis (AD) including skin inflammation, pruritis and severe dermatitis [6] and [18] and IL-31 levels in serum or at mRNA level may be a valuable indicator of allergic asthma [19]. IL-31 is known to act through a hetero-dimeric Chlormezanone receptor composed of IL-31 receptor A (IL-31RA) and oncostatin M receptor (OSMR), which has been shown to activate signal transducer and activator of transcription factor 3 (STAT-3) in alveolar epithelial cells transfected with IL-31-RA, a pathway shared

by IL-9 which has also been implicated in goblet cell hyperplasia and airways remodelling [20], [21] and [22]. IL-31 activates STAT-1 and STAT-5 to a lesser extent [23] and [24], a similarity shared with IL-9. IL-31 has been shown to significantly increase epidermal growth factor (EGF) in a transformed human bronchial epithelial cell line which is linked with up-regulation of mucin transcription [25] and [26]. Human bronchial epithelial cells have been shown to express IL-31-RA and are thought to be direct targets for IL-31 [20]. It is important therefore to study IL-31 further, in a human paediatric epithelial cell model [27] to identify its effect on paediatric airways.