The Investigation of Reovirus Induced Thymic Stromal Lymphoietin Expression through the Analysis of NF-Kb and Its Link in the Signaling Pathway

A cytokine known as thymic stromal lymphoietin (TSLP) is produced by non-hematopoietic cells in the body by the epithelial cells to promote the maturation of dendritic cells. Dendritic cells are major players in both innate and adaptive immune responses by mediating the responses of T-cells, particularly Th2 responses. Preliminary experiments demonstrated that reovirus, a virus that commonly infects the intestine, could stimulate intestinal epithelial cells to produce TSLP in vitro. We hypothesize that reovirus induces TSLP production through activation of the nuclear factor-κB (NF-κB) signaling pathway, where NF-κB is a protein complex that controls DNA transcription in cellular systems. To test this hypothesis, we assess TSLP production in reovirus-stimulated intestinal epithelial cell lines including iCCL2 and MODE-K, while disrupting NF-κB signaling by genetic and chemical methods including introduction of silencing RNA (siRNA) and specific chemical inhibitors of NF-κB activation such as CAPE and IKK inhibitor-VII (IKKi-VII). Our studies aim to delineate mechanisms by which epithelial cells respond to virus infection and initiate protective immune responses.