Vectorial secretion of interleukin-8 (IL-8 or CXCL8) mediates homeostatic effects on the intestinal epithelium via apically located CXCR1

CXCL8 is produced by many cell types including epithelial, endothelial, fibroblasts and macrophages in response to TLR recognition of microbe-associated molecular patterns (MAMPs) or inflammatory cytokines and recruits phagocytes from the vasculature to sites of infection via interaction with its cognate receptors CXCR1 and CXCR2. In the intestine, CXCL8 has been demonstrated to participate in the migration of neutrophils across the epithelium during acute inflammation. Given the well-recognized role of CXCL8 as an initiator of inflammation and the constant presence of commensal bacteria in the intestinal tract, we hypothesized that in the intestinal epithelium, CXCL8 might be secreted in a vectorial fashion depending on the location and type of stimulus as a mechanism to maintain homeostasis. In addition, we hypothesized that the CXCR1 receptor might control specific functions in polarized IECs depending on its location. We tested these hypotheses using microarray gene expression profiling of IL-8 treated and mock-treated Caco-2 cell line