We concluded that oral tolerance for food antigens is induced in two ways: (i) by initial exposure to antigen, or inherent tolerance, and (ii) by transfer of Tregs, or acquired tolerance. Because food allergies occur when inherent tolerance is absent, understanding of acquired tolerance is important for the development of therapies for food allergy.

HighlightsWe generated SMP30/SOD1-double knockout (DKO) mice for oxidative stress research.SMP30/SOD1-DKO mice showed low levels of ascorbic acid and premature death.SMP30/SOD1-DKO mice exhibited high levels of oxidative stress and liver injury.SMP30/SOD1-DKO mice manifest hepatic steatosis due to decreased levels of Apolipoprotein B.

Abstract. Flavonoids are biologically active polyphenolic compounds widely distributed in plants. Recent research has focused on high dietary intake of flavonoids because of their potential to reduce the risks of diseases such as cardiovascular diseases, diabetes, and cancers. We report here the effects of plant flavonoids on catecholamine signaling in cultured bovine adrenal medullary cells used as a model of central and peripheral sympathetic neurons. Daidzein (0.01 -1.0 mM), a soy isoflavone, stimulated 14 C-catecholamine synthesis through plasma membrane estrogen receptors. Nobiletin (1.0 -100 mM), a citrus polymethoxy flavone, enhanced 14 Ccatecholamine synthesis through the phosphorylation of Ser19 and Ser40 of tyrosine hydroxylase, which was associated with 45 Ca 2+ influx and catecholamine secretion. Treatment with genistein (0.01 -10 mM), another isoflavone, but not daidzein, enhanced [ 3 H]noradrenaline uptake by SK-N-SH cells, a human noradrenergic neuroblastoma cell line. Daidzein as well as nobiletin (≥ 1.0 mM) inhibited catecholamine synthesis and secretion induced by acetylcholine, a physiological secretagogue. The present review shows that plant flavonoids have various pharmacological potentials on the catecholamine system in adrenal medullary cells, and probably also in sympathetic neurons.

The effect of 10-hydroxy-trans-2-decenoic acid (10H2DA), a major fatty acid component of royal jelly, was investigated on LPS-induced cytokine production in murine macrophage cell line, RAW264 cells. 10H2DA inhibited LPS-induced IL-6 production dose-dependently, but did not inhibit TNF-α production. 10H2DA inhibited LPS-induced NF-κB activation in a dose-dependent fashion. In addition, NF-κB activation induced by over-expression of either MyD88 or Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) was also inhibited by 10H2DA. Degradation of IκB-α and phosphorylation of IκB kinase-α were not inhibited by 10H2DA. On the other hand, reduction of LPS-induced IκB-ζ expression was discovered. Production of lipocalin-2 and granulocyte colony-stimulating factor (G-CSF), which is dependent on IκB-ζ, was also inhibited by 10H2DA, whereas that of IκB-ζ-independent cytokines/chemokines, such as IFN-β, murine monocyte chemotactic protein-1 (JE), macrophage inflammatory protein (MIP)-1α and MIP-2, was not. Together, 10H2DA specifically inhibited LPS-induced IκB-ζ expression, followed by inhibition of IκB-ζ-dependent gene production. These results suggest that 10H2DA is one of the components of royal jelly to show anti-inflammatory effects and could be a therapeutic drug candidate for inflammatory and autoimmune diseases associated with IκB-ζ and IL-6 production.

Royal jelly is a food for queen and larvae honeybees. 10-Hydroxy-trans-2-decenoic acid (10H2DA; "royal jelly acid") is the principal lipid component in royal jelly. Several pharmacological activities of 10H2DA have been reported: anti-tumor, anti-biotic, immunomodulatory, estrogenic and neurogenic. We recently revealed an inhibitory effect of 10H2DA in innate immune signals. Despite appreciable advances in studies on innate immune signals after the identification of Toll-like receptors as innate immune receptors, few studies have reported the effect of 10H2DA on innate immune signals. In this review, we focus on recent advances in the evaluation of the biological activities of 10H2DA (especially immunomodulatory activities). We also discuss the molecular mechanisms underpinning these biological activities, which could lead to new therapeutic targets for the treatment of immune disorders.

Royal jelly acid, 10-hydroxy-trans-2-decenoic acid (10H2DA), is a major lipid component of royal jelly, which is the exclusive diet of queen honeybees. Previously, we showed partial inhibition of lipopolysaccharide (LPS)-induced NF-κB activation by 10H2DA. In this study, the ability of 10H2DA to inhibit LPS-induced nitric oxide (NO) production was investigated. LPS-induced NO production and inducible NO synthase (iNOS) gene transcription were inhibited by 10H2DA. LPS-stimulated interferon (IFN)-β production, IFN regulatory factor-1 induction and IFN-stimulated response element activation, which are required for iNOS induction, were unaffected by 10H2DA. IFN-β-induced NO production, however, was significantly inhibited by 10H2DA. Furthermore, IFN-β-induced nuclear factor (NF)-κB activation and tumour necrosis factor (TNF)-α production were significantly inhibited by 10H2DA, and TNF-α-induced NF-κB activation was also inhibited by 10H2DA. These results and our previous study suggest that 10H2DA inhibits LPS- and IFN-β-induced NO production via inhibition of NF-κB activation induced by LPS or IFN-β.

In this study, we determined that α-tocopherol levels and hepatic α-TTP protein levels of mice undergo significant tissue-specific, age-related changes. This is the first report to investigate VE in terms of the α-tocopherol levels in plasma and various tissues of mice and hepatic α-TTP protein levels during aging.

The alternatively spliced isoform of nonmuscle myosin II heavy chain B (MHC-IIB) with an insert of 21 amino acids in the actin-binding surface loop (loop 2), MHC-IIB(B2), is expressed specifically in the central nervous system of vertebrates. To examine the role of the B2 insert in the motor activity of the myosin II molecule, we expressed chimeric myosin heavy chain molecules using the Dictyostelium myosin II heavy chain as the backbone. We replaced the Dictyostelium native loop 2 with either the noninserted form of loop 2 from human MHC-IIB or the B2-inserted form of loop 2 from human MHC-IIB(B2). The transformant Dictyostelium cells expressing only the B2-inserted chimeric myosin formed unusual fruiting bodies. We then assessed the function of chimeric proteins, using an in vitro motility assay and by measuring ATPase activities and binding to F-actin. We demonstrate that the insertion of the B2 sequence reduces the motor activity of Dictyostelium myosin II, with reduction of the maximal actin-activated ATPase activity and a decrease in the affinity for actin. In addition, we demonstrate that the native loop 2 sequence of Dictyostelium myosin II is required for the regulation of the actin-activated ATPase activity by phosphorylation of the regulatory light chain.