Oral Use of Interferon-α Stimulates ISG-15 Transcription and Production by Human Buccal Epithelial Cells

Document Type

Article

Publication Date

9-6-1999

Description

ISG-15 is a 15-kDa protein encoded by an interferon (IFN)-stimulated gene (ISG), which is transcriptionally regulated by IFN-α and IFN-β. Considered as part of the cytokine network, ISG-15 has the potential to amplify the immunomodulatory effects of these IFNs by enhancing IFN-γ production, natural killer cell proliferation, and lymphokine-activated killer cell cytotoxicity. To understand better the mechanism(s) of action of orally administered IFN-α, we have studied the effect of IFN-α on ISG-15 gene expression by human buccal epithelial cells (BEC). For in vitro studies, ISG-15 mRNA and protein levels were measured in BEC incubated for 0.5, 2, and 9 h with 100 or 1,000 IU/ml of human lymphoblastoid IFN-α. For in vivo studies, ISG-15 mRNA was measured in BEC samples collected at baseline, and 0.5, 2, and 9 h after 5-20 min of oral rinsing with 10 ml of IFN-α (1,000 IU/ml). ISG-15 mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR), and ISG-15 protein production by Western Blot analysis. IFN-α augmented BEC ISG-15 gene expression in a concentration dependent manner both in vivo and in vitro. We conclude that orally administered IFN-α exerts its immunomodulatory effects in humans in part by upregulating the production of ISG15 by BEC, thereby enhancing the immune reactivity of mucosa-associated lymphocytes.

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