title: Evidence for the immunostimulatory effects of low-dose orally delivered human IFN-alpha in cattle.
abstract: Orally delivered interferon-alpha (IFN-alpha) has been associated with systemic protection against various disorders in humans and animals. In an attempt to understand how IFN-alpha delivers a systemic signal following its local oral administration, the present study aimed at identifying genes differentially regulated in bovine peripheral blood through the use of cDNA microarrays following oral therapy with IFN-alpha. We identified thousands of genes to be IFN-alpha regulated. Of these, about 8.5% had a minimum 4-fold degree of change, the majority of which represented novel IFN-stimulated genes (ISG). Several upregulated ISGs were transcripts with key and diverse biologic functions, including antigen processing and presentation, leukocyte migration, lymphocyte activation, immune effector and modulation functions, apoptosis, and hematopoiesis. Interestingly, IFN-alpha expression itself was not modulated in bovine peripheral blood, suggesting that the blood levels of IFN-alpha are not the hallmark of the immunostimulatory effects of oral IFN-alpha therapy. Rather, IFN-alpha seems to interact with local mucosal lymphoid cells in the gastrointestinal tract. This interaction may initiate a signaling cascade eventually leading to the transcriptional induction of ISGs, which in turn encode immunostimulatoiry proteins. Thus, ISGs, through the proteins they encode, may potentially perform critical immune modulation functions.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, 2-13 Inada, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Boniface
authors.initials: B
authors.lastname: Namangala
authors.forename: Noboru
authors.initials: N
authors.lastname: Inoue
authors.forename: Junko
authors.initials: J
authors.lastname: Kohara
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kuboki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sakurai
authors.forename: Kyouko
authors.initials: K
authors.lastname: Hayashida
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sugimoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D020869:Gene Expression Profiling; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000502:physiology; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha