Modulation of Immunity-Related Gene Expression in Small Intestines of Mice by Oral Administration of Lactoferrin

Abstract
Oral administration of lactoferrin (LF), an antimicrobial and immunomodulatory protein, shows a protective effect against infectious diseases, possibly via immunomodulation of the host. Initially, we confirmed an immunomodulatory effect of LF by observing changes in the number of cells in the leukocyte subsets in the peripheral blood and spleens of mice 1 day after oral administration of LF. Then we developed a quantitative reverse transcription-PCR method for 20 immunity-related genes of antimicrobial proteins, pattern recognition receptors, cytokines, and lymphocyte mobilization-related proteins, and we assessed the expression of these genes in the small intestines of mice 2 h after administration of water, bovine serum albumin (BSA), or LF. Expression of the LF gene was lower in mice administered LF than in mice administered water or BSA, implying a negative-feedback control. Expression of gamma interferon (IFN-γ) and interleukin-10 (IL-10) was lower in both BSA- and LF-administered mice than in water administered mice, suggesting a nonspecific effect of protein ingestion. Expression of NOD2, IFN-β, and IL-12p40 was higher with LF administration than with water or BSA administration. The expression levels of these three genes were correlated. This study indicated that oral administration of LF modulates the small intestinal expression of genes closely related to the host defense in a specific or a nonspecific manner.