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-␥) 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-␤, 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.

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

“…Lactoferrin has the potential to promote development of both T H 1 and T H 2 immune responses, depending on experimental conditions [29,30]. Towards its utility as an adjuvant, in vivo and in vitro studies indicate that lactoferrin can increase relative production of IL-12 while decreasing IL-10, a negative regulator of IL-12 [19,[31][32][33]. Of critical importance, bovine lactoferrin added to murine macrophages infected with BCG enhanced the production of IL-12 relative to amounts of IL-10 [34].…”

Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis

“…Lactoferrin possesses a wide range of immunomodulatory activities [17][18][19] [20] [21] including promotion of the T-cell dominated DTH response towards BCG antigens [22,23], The ability of lactoferrin to enhance the generation of antigen specific DTH responses suggests that lactoferrin could promote development of specific T-cell responses against a complex antigen, such as BCG [24,25] The development of T-cell helper type 1 (T H 1) immunity is, in part, regulated by production of IL-12 [26,27]. A variety of in vivo studies have shown lactoferrin capable of increasing production of IL-12 [28][29][30]. IL-12 is clearly a critical component involved in directing T H 1 development effective in promoting protective host responses during MTB infection [31,32].…”

Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes

“…Thus, a high IL-12:IL-10 ratio from activated macrophages is indicative of a cytokine environment that is favored towards promotion of T H 1 immunity. A limited number of studies have shown increasing IL-12 with concurrent decrease of IL-10 levels following administration of Lactoferrin [44,46,47]. Lactoferrin also demonstrated direct in vivo stimulatory activity in naïve mice with recovered peritoneal cells from mice injected with Lactoferrin exhibiting increased in TNF-α, IL-6, and IL-12 production [1].…”