Resveratrol (trans-3,5,4Ј-Trihydroxystilbene) Ameliorates Experimental Allergic Encephalomyelitis, Primarily via Induction of Apoptosis in T Cells Involving Activation of Aryl Hydrocarbon Receptor and Estrogen Receptor

ABSTRACT Resveratrol (trans-3,5,4Ј-trihydroxystilbene), a polyphenolic compound found in plant products, including red grapes, exhibits anticancer, antioxidant, and anti-inflammatory properties

Role of Myeloid-Derived Suppressor Cells in Amelioration of Experimental Autoimmune Hepatitis Following Activation of TRPV1 Receptors by Cannabidiol

Myeloid-derived suppressor cells (MDSCs) are getting increased attention as one of the main regulatory cells of the immune system. They are induced at sites of inflammation and can potently suppress T cell functions. In the current study, we demonstrate how activation of TRPV1 vanilloid receptors can trigger MDSCs, which in turn, can inhibit inflammation and hepatitis.Polyclonal activation of T cells, following injection of concanavalin A (ConA), in C57BL/6 mice caused acute hepatitis, characterized by significant increase in aspartate transaminase (AST), induction of inflammatory cytokines, and infiltration of mononuclear cells in the liver, leading to severe liver injury. Administration of cannabidiol (CBD), a natural non-psychoactive cannabinoid, after ConA challenge, inhibited hepatitis in a dose-dependent manner, along with all of the associated inflammation markers. Phenotypic analysis of liver infiltrating cells showed that CBD-mediated suppression of hepatitis was associated with increased induction of arginase-expressing CD11b(+)Gr-1(+) MDSCs. Purified CBD-induced MDSCs could effectively suppress T cell proliferation in vitro in arginase-dependent manner. Furthermore, adoptive transfer of purified MDSCs into naïve mice conferred significant protection from ConA-induced hepatitis. CBD failed to induce MDSCs and suppress hepatitis in the livers of vanilloid receptor-deficient mice (TRPV1(-/-)) thereby suggesting that CBD primarily acted via this receptor to induce MDSCs and suppress hepatitis. While MDSCs induced by CBD in liver consisted of granulocytic and monocytic subsets at a ratio of ∼2∶1, the monocytic MDSCs were more immunosuppressive compared to granulocytic MDSCs. The ability of CBD to induce MDSCs and suppress hepatitis was also demonstrable in Staphylococcal enterotoxin B-induced liver injury.This study demonstrates for the first time that MDSCs play a critical role in attenuating acute inflammation in the liver, and that agents such as CBD, which trigger MDSCs through activation of TRPV1 vanilloid receptors may constitute a novel therapeutic modality to treat inflammatory diseases

Anaphylaxis caused by the ingestion of cultivated mushroom (Agaricus bisporus): Identification of allergen as mannitol

ABSTRACTBackgroundThe role of mushroom spores as inhalants in causing respiratory allergy has been well established. Although mushrooms are commonly used as food throughout the world, food allergy to mushrooms is not very common. A severe case of anaphylaxis in a 32-year-old woman who experienced facial edema and generalized urticaria minutes after eating mushroom curry is presented herein. The purpose of the present study was to identify the putative allergen in the cultivated mushroom Agaricus bisporus.MethodsA combination of biochemical fractionation/ analytical techniques (gel filtration, ultrafiltration, ion-moderated cation-exchange chromatography, high-pressure liquid chromatography and gas chromatography–mass spectrometry (GC-MS)) and allergy diagnostic tests (skin prick test (SPT), allergen-specific IgE) were used.ResultsThe SPT with mushroom extract was strongly positive; however, allergen-specific IgE could not be detected by enzyme-linked immunosorbent assay. The SPT was also positive with cooked, steamed or dried mushroom extracts, suggesting the presence of a heat-stable allergen. Gel filtration of mushroom extract on Sephadex G-25, as analyzed by SPT, indicated the presence of a low molecular weight (<1 kDa) allergen. Using ion-moderated cation-exchange chromatography, the allergen was isolated and identified as mannitol based on skin reactivity. Mannitol was confirmed by GC-MS analysis.ConclusionsThis is the first report of food allergy to cultivated mushroom A. bisporus and also the first report describing a low molecular weight allergen (mannitol) in mushroom

Characterization and Gene Cloning of an Acidic Thaumatin-Like Protein (TLP 1), an Allergen from Sapodilla Fruit (Manilkara zapota)

Background: Allergy to sapodilla (Manilkara zapota) fruit ingestion is rare. An independent study from our group has identified a basic thaumatin-like protein (TLP 2) as the major allergen. The present study was aimed at identifying and characterizing additional allergens from sapodilla. Methods: Allergic subjects were identified by case history, skin prick test (SPT) and allergen-specific IgE. Sapodilla extract was fractionated using SP-Sepharose into 3 components (SP1, SP2 and SP3) which were analyzed by native/SDS-PAGE, IgE-immunoblot, isoelectric focusing (IEF) and N-terminal sequencing. The conserved regions of plant TLPs and the N-terminal sequence were used to design primers for PCR. Results: SPT and ELlSA confirmed a subject with oral allergy syndrome (OAS) to sapodilla and custard apple. Two proteins (26.9 and 24.5 kDa; reducing conditions) were detected as allergens, of which the latter in SP2 has already been identified as basic TLP (TLP 2). The 26.9 kDa protein present in SP1 was identified as an acidic TLP based on native PAGE, IEF and N-terminal sequencing. Presence of a basic β-1,3-glucanase in SP3 was inferred by zymography. Sequence analysis of the genomic clone of the acidic TLP gene revealed that it is intronless and non-glycosylated. Evolutionary relatedness to olive, grape and kiwi fruit allergenic TLPs were inferred by phylogenetic analysis. Conclusions: An acidic TLP (TLP 1) was identified as a new allergen in sapodilla. TLP 1 is a single polypeptide (207 residues) belonging to the thaumatin family of the GH64-TLP-SF superfamily. Clinically, sapodilla should be considered in the list of fruits causing OAS

Characterization of MDSCs in liver.

<p>Liver infiltrating cells isolated from indicated treatment groups (n = 4) were triple-stained for CD11b, Gr-1 and intracellular arginase 1. Respective histograms (filled) for arginase expression on CD11b⁺Gr-1⁺ gated cells are shown for each group with respective MFI (A). Open histograms represent staining control. B) Arginase functional activity was determined by spectrophotometric assay using lysates of liver infiltrating cells from each group. Data are mean ± SEM (n = 4). Student's <i>t</i>-test, **p<0.01. C) Immunohistochemistry for arginase expression in liver sections and D) Morphology of infiltrating liver cells by Wright Giemsa staining (a. Veh, b. CBD, c. ConA+veh, d. ConA+CBD).</p