Abstract
Interferon-alpha (IFN-α) shows potent immunomodulatory properties, which underlies its use for low-dose oral treatments of diverse viral infections and immunopathological conditions. The studies on oral administration have been hampered by the lack of recognized in vitro models, reproducing the in vivo control action of IFN-α over inflammatory cytokine responses. Owing to these reasons, the aim of our study was to validate IPEC-J2 (a continuous cell line of porcine intestinal epithelial cells) as a reporter system of the properties of IFN-α. Three different experimental conditions (oxidative stress, inflammatory response, and amplification of lymphoid cell signals) were selected to evaluate the effects of porcine recombinant IFN-α1 (rIFN-α) and 2 natural porcine IFN-α preparations (nIFN-α). The IFNs under study showed significantly different control actions in IPEC-J2 cells. In particular, rIFN-α was shown to down-regulate interleukin (IL)-8, IL-1β, tumor necrosis factor (TNF)-α, and β-defensin 1 genes either directly, or indirectly through second messengers released by IFN-α-treated lymphoid cells. With regard to IL-6, only second messengers from IFN-α-treated lymphoid cells could regulate the expression of this cytokine. Our results suggest that IPEC-J2 cells can be a useful tool for investigating the regulatory actions of type I IFNs and the second messengers thereof. The results provided by this model could be conveniently exploited in studies on enteric diseases sustained by infectious or noninfectious stressors.