Chemokines Induced in Human Respiratory Epithelial Cells by IL-1 Family of Cytokines

IL-1-related cytokines share similarities in their receptor distribution and signalling pathways; however, overlapping actions of these cytokines have not been clearly demonstrated. The aim of our study was to compare the capacity of different IL-1-related cytokines to stimulate production and release of multiple CC and CXC chemokines by epithelial cells. The chemokine gene expression was studied using a cDNA array system in human alveolar type-II like cells A549 stimulated by IL-1 beta, IL-18, and IL-33. The chemokine levels in culture supernatants were measured using multiplex immunoluminometric assay or by ELISA. In repetitive experiments, in response to IL-1 beta epithelial cells expressed mRNA for CCL2, CCL5, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, and CXCL11. In contrast, induction of epithelial cells by IL-33 and IL-18 resulted only in moderate up-regulation of a few CC or CXC chemokines compared to the potent effect of IL-1 beta stimulation. We conclude from our data that individual members of the IL-1 family, although related in molecular structure and signalling pathways, widely differ in their capacity to stimulate epithelial production of both CXC and CC chemokines.