Etsuko Harada

Montelukast suppresses epithelial to mesenchymal transition of bronchial epithelial cells induced by eosinophils.

Epithelial to mesenchymal transition (EMT) is a mechanism by which eosinophils can induce airway remodeling. Montelukast, an antagonist of the cysteinyl leukotriene receptor, can suppress airway remodeling in asthma. The purpose of this study was to evaluate whether montelukast can ameliorate airway remodeling by blocking EMT induced by eosinophils. EMT induced was assessed using a co-culture system of human bronchial epithelial cells and human eosinophils or the eosinophilic leukemia cell lines, Eol-1. Montelukast inhibited co-culture associated morphological changes of BEAS-2b cells, decreased the expression of vimentin and collagen I, and increased the expression of E-cadherin. Montelukast mitigated the rise of TGF-β1 production and Smad3 phosphorylation. Co-culture of human eosinophils with BEAS-2B cells significantly enhanced the production of CysLTs compared with BEAS-2B cells or eosinophils alone. The increase of CysLTs was abolished by montelukast pre-treatment. Montelukast had similar effects when co-culture system of Eol-1 and BEAS-2B was used. This study showed that montelukast suppresses eosinophils-induced EMT of airway epithelial cells. This finding may explain the mechanism of montelukast-mediated amelioration of airway remodeling in bronchial asthma.

Termitomycamides A to E, fatty acid amides isolated from the mushroom Termitomyces titanicus, suppress endoplasmic reticulum stress.

Five fatty acid amides, termitomycamides A to E (1 to 5), were isolated from the giant edible mushroom Termitomyces titanicus. The structures of 1-5 were determined by the interpretation of spectral data and/or synthesis. Compounds 2 and 5 showed protective activity against endoplasmic reticulum stress-dependent cell death.

A mushroom-derived amino acid, ergothioneine, is a potential inhibitor of inflammation-related DNA halogenation.

Myeloperoxidase (MPO)-generated halogenating molecules, such as hypochlorous acid and hypobromous acid (HOBr), in inflammatory regions are postulated to contribute to disease progression. In this study, we showed that ergothioneine (EGT), derived from an edible mushroom, inhibited MPO activity as well as the formation of 8-bromo-2′-deoxyguanosine in vitro. The HOBr scavenging effect of EGT is higher than those of ascorbic acid and glutathione. We initially observed that the administration of Coprinus comatus, an edible mushroom containing a high amount of EGT, inhibited the UV-B-induced inflammatory responses and DNA halogenation, suggesting that EGT is a promising anti-inflammatory agent from mushrooms. Graphical abstract The ergothioneine-rich Coprinus extract inhibited both MPO activity and HOBr-induced DNA damage in addition to inhibition of UV-B-induced inflammatory responses.

Effect of the Medicinal Mushroom, Grifola gargal (Agaricomycetes), on Bone Turnover Markers and Serum Lipids in Middle-Aged and Elderly Japanese Women.

A clinical study was performed to examine the effect of the edible mushroom, Grifola gargal, on bone turnover markers and serum lipids in middle-aged and elderly Japanese women. Postmenopausal women aged 51-73 years (mean age, 61 years) received daily oral administration of 5 g G. gargal fruiting bodies (hot air-dried and powdered; G. gargal powder [GGP]). Serum levels of bone alkaline phosphatase (BAP) and lipids and urinary deoxypyridinoline (DPD) levels were measured before and 2 weeks after the start of GGP treatment. As a result, urinary DPD bone resorption marker levels in women treated with GGP decreased significantly. Serum levels of the BAP bone formation marker also tended to increase, but the difference was not significant. By contrast, the atherogenic index decreased and the high-density lipoprotein (HDL) ratio increased significantly. However, there were no statistically significant differences in serum lipids of total cholesterol, HDL cholesterol, and low-density lipoprotein cholesterol. In addition, this study demonstrated for the first time that G. gargal is safe for human consumption.

Novel Cerebroside, Termitomycesphin I, from the Mushroom, Termitomyces titanicus

The novel cerebroside, termitomycesphin I (1), and two known cerebrosides (2 and 3) were isolated from the edible mushroom, Termitomyces titanicus. The structures of 1–3 were determined and identified by interpreting the spectroscopic data.

Activated protein C modulates the proinflammatory activity of dendritic cells

Background Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. Materials and methods Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. Results Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C-treated ovalbumin-pulsed dendritic cells had significantly less airway hyperresponsiveness, significantly decreased lung concentrations of Th1 and Th2 cytokines, and less plasma concentration of immunoglobulin E when compared to control mice. Conclusion These results suggest that dendritic cells mediate the immunosuppressive effect of activated protein C during allergic inflammation.

A Blood Sugar Level-Reducing Effect and a Fat-Reducing Effect of a Novel Medicinal Mushroom, Grifola gargal (Agricomycetes)

Grifola gargal Singer is a medicinal mushroom with biological effects such as antiatherogenic and antiosteoporotic activities. The objective of this study was to examine a blood glucose-reducing effect and a fatreducing effect of G. gargal supplementation in vivo. The effects of G. gargal powder (GGP) in a high-molecular weight hot water extract (GGH) and a low-molecular weight hot water extract (GGL) on blood glucose were investigated in streptozotocin (STZ)-induced diabetic ICR mice (STZ diabetic mice). A significant decrease in blood glucose was observed after 5 weeks of GGL supplementation (fraction with a molecular weight ≤ 6000 Da) in STZ diabetic mice. In the next test, we examined the antihyperglycemic and fat-reducing effects of GGL in diet-induced obesity (DIO) mice fed a high-fat diet. GGL facilitated reductions in blood glucose and body fat. This study confirms, to our knowledge for the first time, that administration of G. gargal extract has antihyperglycemic and body fat-reducing effects in STZ diabetic mice and DIO mice. Therefore, G. gargal is a promising functional food to prevent and treat diabetes and lifestyle-related diseases.