ROTAVIRUS INFECTION OF CULTURED INTESTINAL EPITHELIAL-CELLS INDUCES SECRETION OF CXC AND GC CHEMOKINES

Background & Aims: Rotaviruses are the major cause of pediatric gastro enteritis worldwide. The target cell of rotavirus infection is the mat ure enterocyte of the small intestine. Recently, intestinal epithelial cells have been shown to produce chemoattractant mediators in respons e to cytokine stimulation and bacterial infection, suggesting a potent ially important role of epithelial cells in initiating immune response s. In this study, the production of chemokines by cultured intestinal epithelial cells after rotavirus infection was investigated. Methods: Two human intestinal epithelial cell lines (HT29 and Caco-2) were infe cted with sucrose-purified rotavirus (strain SA114F) and assayed by re verse-transcription polymerase chain reaction and enzyme-linked immuno sorbent assay for chemokine expression. Virus-like particles and inact ivated rotavirus were used to test the importance of viral attachment and replication. Results: Increased messenger RNA expression and secre tion of immunoreactive interleukin 8, growth-related peptide alpha, an d RANTES (regulated upon activation, normal T cell expressed and secre ted) were detected in rotavirus-infected cells. Chemokine production w as time and dose dependent and required viral replication. Conclusions : Rotavirus infection induces the expression of a subset of chemokines in intestinal epithelial cells. These data support the hypothesis tha t chemokine secretion by enterocytes may play a role in the initiation and modulation of the immune response to rotavirus infection.