Kaoru Akatani

Antiallergic Effects of Lactobacillus pentosus Strain S-PT84 Mediated by Modulation of Th1/Th2 Immunobalance and Induction of IL-10 Production

Background: Many types of fermented food are consumed in Japan. Although some are produced by plant-origin lactic-acid bacteria (LAB) fermentation, the physiological functions of such bacteria remain unclear. We therefore isolated LAB of plant origin from Kyoto pickles and determined the immunological activity of heat-killed preparations of plant-origin LAB. Methods: The Lactobacillus pentosus strain S-PT84 was selected from among 16 LAB of plant origin as the strongest interleukin (IL)-12-inducing strain. IL-12- and IL-10-inducing activities were determined with macrophages from BALB/c mice. The in vivo immunomodulating effect of S-PT84was determined with BALB/c mice fed S-PT84. The antiallergic activity of S-PT84 was examined in ovalbumin (OVA)/alum-administered BALB/c mice. Results: The L. pentosus strain S-PT84 induced production of both IL-12 and IL-10 in vitro. S-PT84 enhanced splenic natural-killer activity and modulated the T helper (Th) type 1/type 2 balance toward a Th1-dominant state. In the OVA-induced allergy model, orally administered S-PT84 lowered serum IgE levels and suppressed active cutaneous anaphylaxis reaction and splenic IL-4 production. IL-10 production from splenocytes of OVA-immunized mice was upregulated by feeding S-PT84. Conclusions: Despite heat-killing, S-PT84 exhibited antiallergic effects by modulating the Th1/Th2 balance and inducing regulatory T cells. The L. pentosus strain S-PT84, which is of plant origin and isolated from a traditional Japanese food, is expected to be useful for treatment of many immune diseases including allergies, tumors, infectious diseases and auto-immune diseases.

Isolation and molecular characterization of a serotype 9 human rotavirus strain.

A human rotavirus strain, designated AU32, that belongs to serotype 9 was isolated and was compared by RNA‐RNA hybridization with recently established two serotype 9 strains (WI61 and F45) as well as other prototype human strains. These three strains exhibited a very high degree of homology with one another and shared a high degree of homology with strains belonging to the Wa genogroup but not with strains belonging to either the DS‐1 or AU‐1 genogroup. These results suggest that genetic constellation of the serotype 9 strains is similar to that of the commonest human rotavirus despite the recent recognition of this serotype.

Effect of Lactobacillus pentosus S-PT84 Ingestion on IFN-α Production from Plasmacytoid Dendritic Cells by Virus Stimulation

We investigated the effect of ingesting Lactobacillus pentosus S-PT84 on the interferon-α (IFN-α) production from splenocytes and plasmacytoid dendritic cells by virus stimulation. IFN-α production by the Lactobacillus pentosus S-PT84 ingestion group was significantly greater under the virus-infected condition than that by the control group. Lactobacillus pentosus S-PT84 could enhance the production of IFN-α which is known as an important cytokine for preventing virus infection. It may therefore become a prophylactic tool against such virus infection.

Abstract 2695: Lactobacillus plantarum induces TRAIL production and facilitates natural killer activity against cancer cells

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-tumor agent due to its induction of apoptosis in various types of malignant tumor cells with little or no toxicity in normal cells. TRAIL is an endogeneous cytokine, and thus, it may be possible to develop agents that can induce endogeneous TRAIL production as an anti-tumor strategy. Here, we show for the first time that lactobacilli induce TRAIL production in normal human peripheral blood mononuclear cells (PBMC). Treatment with heat-killed Lactobacillus (L.) plantarum, a type of lactobacilli, induced TRAIL expression on the surface of PBMC. L. plantarum also enhanced the release of soluble TRAIL into the culture medium. Moreover, L. plantarum increased the level of TRAIL mRNA as well as TRAIL protein, indicating that L. plantarum up-regulates TRAIL gene expression. L. plantarum also increased the secretion of interferon-γ (IFN-γ) from PBMC. The release of soluble TRAIL from PBMC was partially blocked by IFN-γ neutralization antibody, indicating that the TRAIL production induced by L. plantarum at least partially depends on IFN-γ. To examine whether TRAIL production by L. plantarum leads to cytotoxicity in cancer cells, we co-cultured prostate cancer cells with L. plantarum-treated PBMC and measured natural killer (NK) activity. L. plantarum facilitated NK activity, and the dominant negative form of TRAIL receptor and TRAIL neutralization antibody efficiently prevented NK activity. Our results indicate that L. plantarum facilitates TRAIL-dependent NK activity through TRAIL production, and raise the possibility of a new strategy for TRAIL-based prevention or therapy against malignant tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2695. doi:10.1158/1538-7445.AM2011-2695