stilbenes and Hypersensitivity

In this study, the role and mechanism of pterostilbene (Pts) in mast cell degranulation in vitro and in vivo were investigated. The results showed that Pts inhibited mast cell-mediated local passive allergic reactions in mice. In addition, treatment with Pts reduced both histamine release and calcium influx in rat peritoneal mast cells and RBL-2H3 cells and reduced IgE-mediated mast cell activation. Furthermore, the mechanism underlying Pts inhibition of mast cell signaling was probed via studying the effects of Pts on liver kinase B1 (LKB1), including the use of the LKB1 activator metformin and siRNA knockdown of LKB1. The data showed that Pts reduced the release of inflammatory mediators such as tumor necrosis factor-α, interleukin-6, leukotriene C4, and prostaglandin D2 in mast cells by activating the LKB1/adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Furthermore, Pts inhibited phosphorylation of FcεRI and FcεRI-mediated degranulation in RBL-2H3 cells. These effects were attenuated after LKB1 knockdown. Taken together, Pts could inhibit FcεRI signaling through activation of the LKB1/AMPK signaling pathway in IgE-mediated mast cell activation. Thus, Pts might be an effective therapeutic agent for mast cell-mediated allergic diseases.

Topics: AMP-Activated Protein Kinases; Animals; Cell Degranulation; Hypersensitivity; Mast Cells; Mice; Rats; Receptors, IgE; Stilbenes

Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal exposure to acrolein abrogated allergen-specific antibody and cytokine formation, and led to a relative accumulation of regulatory T cells in the lungs. Only the acrolein-treated mice were protected from bronchial hyperreactivity as well as from anaphylactic reactions upon challenge with the specific allergen. Moreover, grafted D2F2 tumor cells grew faster and intratumoral Foxp3+ cell accumulation was observed in these mice compared to sham-treated controls. Results from reporter cell lines suggested that acrolein acts via the aryl-hydrocarbon receptor which could be inhibited by resveratrol and 3'-methoxy-4'-nitroflavone Acrolein- stimulation of human PBMCs increased Foxp3+ expression by T cells which could be antagonized by resveratrol. Our mouse and human data thus revealed that acrolein exerts systemic immunosuppression by promoting Foxp3+ regulatory cells. This provides a novel explanation why smokers have a lower allergy, but higher cancer risk.

Topics: Acrolein; Allergens; Animals; Antibody Formation; Cytokines; Disease Models, Animal; Forkhead Transcription Factors; Hypersensitivity; Immunologic Factors; Lung; Mice; Neoplasms; NF-kappa B; Receptors, Aryl Hydrocarbon; Resveratrol; Signal Transduction; Stilbenes; T-Lymphocytes, Regulatory

Peanut sprout is a kind of high quality natural food which has important effect on health-care. It contains abundant bioactive substances such as resveratrol and lower fat. Naturally, resveratrol occurs in stilbene phytoalexin phenolic compound produced in response to a variety of biotic and abiotic stresses. In this study, the influence of ultrasonic stimulation on the resveratrol accumulate in germinant peanut prepared from three varieties (FH12, FH18, and BS1016) in the dry state before steeping were investigated. All experiments were performed using an ultrasonic cleaner bath operating at three frequencies (28, 45 and 100 kHz) for 20 min at constant temperature 30°C. The resulted amounts of resveratrol in peanut sprout were increasing by 2.25, 3.34, and 1.71 times compared with the control group of peanut germinated from FH12, FH18, and BS1016, respectively, after 3d with decreasing the amounts of allergic protein. After ultrasound, the germination rate and total sugar content increased slightly while the crude fat decreased and protein remained unchanged. Overall, the study results indicated that ultrasound treatment combined with germination can be an effective method for producing enriched-resveratrol and poor allergic protein peanut sprout as a functional vegetable.

Topics: Arachis; Carbohydrates; Fatty Acids; Germination; Hypersensitivity; Plant Proteins; Resveratrol; Seeds; Stilbenes; Ultrasonic Waves

The dietary modulation of gut microbiota, suggested to be involved in allergy processes, has recently attracted much interest. While several studies have addressed the use of fibres to modify intestinal microbial populations, information about other components, such as phenolic compounds, is scarce. The aim of this work was to identify the dietary components able to influence the microbiota in 23 subjects suffering from rhinitis and allergic asthma, and 22 age- and sex-matched controls. The food intake was recorded by means of an annual food frequency questionnaire. Dietary fibre tables were obtained from Marlett et al., and the Phenol-Explorer database was used to assess the phenolic compound intake. The quantification of microbial groups was performed using an Ion Torrent 16S rRNA gene-based analysis. The results showed a direct association between the intake of red wine, a source of stilbenes, and the relative abundance of Bacteroides, and between the intake of coffee, rich in phenolic acids, and the abundance of Clostridium, Lactococcus and Lactobacillus genera. Despite epidemiological analyses not establishing causality, these results support the association between polyphenol-rich beverages and faecal microbiota in allergic patients.

Topics: Adult; Asthma; Bacterial Load; Bacteroides; Clostridium; Coffee; Diet; Dietary Fiber; Feces; Female; Flavonoids; Gastrointestinal Microbiome; Humans; Hydroxybenzoates; Hypersensitivity; Lactobacillus; Lactococcus; Male; Middle Aged; Phenols; Rhinitis, Allergic; Stilbenes; Wine

Resveratrol, a natural polyphenol found in the skin of red grapes, is reported to have anti-inflammatory properties including protective effects against aging. Consequently, Resveratrol is a common nutritional supplement and additive in non-prescription lotions and creams marketed as anti-aging products. Studies in mice and with mouse bone marrow-derived mast cells (BMMCs) have indicated anti-allergic effects of Resveratrol. However, the effects of Resveratrol on human primary mast cells have not been reported.. Human mast cells were isolated and purified from normal skin tissue of different donors. The effect of Resveratrol on IgE-dependent release of allergic inflammatory mediators was determined using various immunoassays, Western blotting, and quantitative real-time PCR.. Resveratrol at low concentrations (≤10 μM) inhibited PGD2 biosynthesis but not degranulation. Accordingly, COX-2 expression was inhibited but phosphorylation of Syk, Akt, p38, and p42/44 (ERKs) remained intact. Surprisingly, TNF production was significantly enhanced with Resveratrol. At a high concentration (100 μM), Resveratrol significantly inhibited all parameters analyzed except Syk phosphorylation.. Here, we show that Resveratrol at low concentrations exerts its anti-inflammatory properties by preferentially targeting the arachidonic acid pathway. We also demonstrate a previously unrecognized pro-inflammatory effect of Resveratrol--the enhancement of TNF production from human mature mast cells following IgE-dependent activation.. These findings suggest that Resveratrol as a therapeutic agent could inhibit PGD2-mediated inflammation but would be ineffective against histamine-mediated allergic reactions. However, Resveratrol could potentially exacerbate or promote allergic inflammation by enhancing IgE-dependent TNF production from mast cells in human skin.

Topics: Animals; Cyclooxygenase 2; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Hypersensitivity; Immunoglobulin E; MAP Kinase Signaling System; Mast Cells; Mice; Prostaglandin D2; Resveratrol; Skin; Stilbenes; Tumor Necrosis Factor-alpha

Hovenia dulcis Thunb. (Rhamnaceae) is a hardy tree native to Europe, the Middle East, and North Africa, and it is also grown in parts of Asia and has been used in traditional medicine to treat liver toxicity, stomach disorders, and inflammation. This study investigated the anti-allergy potential of an extract of the branches of H. dulcis (HDB) using the antigen-stimulated mast cell-like cell line rat basophilic leukemia (RBL)-2H3 and a passive cutaneous anaphylaxis (PCA) mouse model. Degranulation assay, reverse transcription PCR, enzyme-lined immunosorbent assays, western blot analyses, and PCA were performed to measure allergic responses and proinflammatory mediators in antigen-stimulated rat basophilic leukemia (RBL)-2H3 mast cells and the PCA mouse model. In antigen-stimulated RBL-2H3 cells, HDB inhibited the secretion of β-hexosaminidase (indicating the inhibition of degranulation) and histamine release; decreased expression and production of the inflammatory mediators, cyclooxygenase-2 and prostaglandin E2, and cytokines interleukin-4 and tumor necrosis factor-α; and suppressed activation of nuclear factor κB, a transcription factor involved in the response to cytokines. HDB attenuated phosphorylation of the mast cell downstream effectors Lyn, Syk, phospholipase Cγ, protein kinase Cμ, extracellular signal-regulated kinase and p38. In IgE-sensitized mice, HDB inhibited mast cell-dependent PCA. Furthermore, HDB contained pinosylvin and possessed significant anti-allergic activities. These results suggest that HDB would be of value in the prevention and treatment of allergic diseases.

Topics: Animals; Anti-Allergic Agents; beta-N-Acetylhexosaminidases; Cell Line, Tumor; Cell Survival; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Hypersensitivity; Immunoglobulin E; Interleukin-4; Mast Cells; Mice; Mice, Inbred BALB C; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Passive Cutaneous Anaphylaxis; Plant Extracts; Rats; Rhamnaceae; Signal Transduction; Stilbenes; Tumor Necrosis Factor-alpha

Oxyresveratrol is known to possess anti-inflammatory property. Current study investigates the immunosuppressive effect of oxyresveratrol by using mouse model of ovalbumin (OVA)-induced allergic airway inflammation.. BALB/c mice were randomly divided into five groups having 8 mice in each group. Treatment with low dose (7 mg/kg) and high dose (15 mg/kg) of oxyresveratrol, and methylprednisolone (15 mg/kg; standard drug) was started 2 week after immunization of mice with ovalbumin and continued for 7d. Ovalbumin was also injected into pinna of right ear 24h before sacrificing the mice to evaluate delayed type hypersensitivity (DTH). H&E and PAS staining were used for histopathological evaluation of lungs. Reverse transcription polymerase chain reaction followed by gel electrophoresis were used for evaluation of mRNA expression levels of IL-4, IL-5, and IL-13.. Oxyresveratrol significantly reduced total leucocyte count in both blood and bronchoalveolar lavage fluid (BALF). Treatment with oxyresveratrol normalized altered eosinophil and neutrophil counts in both blood and BALF. OVA-specific T-cell response was also significantly inhibited by oxyresveratrol. A significant attenuation of inflammatory cell infiltration and goblet cell hyperplasia was observed after treatment with oxyresveratrol. Data showed that oxyresveratrol significantly suppressed Th2 (T helper cells) type immune response which was obvious by the reduction in mRNA expression levels of IL-4, IL-5, and IL-13. Similarly, treatment with methylprednisolone also significantly reduced all the immunomodulatory and inflammatory parameters.. Our study demonstrates that oxyresveratrol ameliorates allergic asthma. The anti-asthmatic activity might in part occur via the down regulation of IL-4, IL-5, and IL-13 expression levels.

Topics: Animals; Bronchoalveolar Lavage Fluid; Hypersensitivity; Interleukin-13; Interleukin-4; Interleukin-5; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Stilbenes; T-Lymphocytes

A complicated interplay between resident mast cells and other recruited inflammatory cells contributes to the development and progression of allergic inflammation entailing the promotion of T helper 2 (Th2) cytokine responses. The current study examined whether resveratrol suppressed the production of inflammatory Th2 cytokines in cultured rat basophilic leukemia RBL-2H3 cells. Cells pre-treated with resveratrol nontoxic at 1–25 μM were sensitized with anti-dinitrophenyl (anti-DNP), and subsequently stimulated by dinitrophenyl-human serum albumin (DNP–HSA) antigen. Resveratrol dose-dependently diminished the secretion of interleukin (IL)-3, IL-4, IL-13 as well as tumor necrosis factor (TNF)-α by the antigen stimulation from sensitized cells. It was found that resveratrol mitigated the phosphorylation of p38 MAPK, ERK, and JNK elevated in mast cells exposed to Fc epsilon receptor I (FcεRI)-mediated immunoglobulin E (IgE)-antigen complex. The FcεRI aggregation was highly enhanced on the surface of mast cells following the HSA stimulation, which was retarded by treatment with 1–25 μM resveratrol. The IgE-receptor engagement rapidly induced tyrosine phosphorylation of c-Src-related focal adhesion protein paxillin involved in the cytoskeleton rearrangement. The FcεRI-mediated rapid activation of c-Src and paxillin was attenuated in a dose-dependent manner. In addition, the paxillin activation entailed p38 MAPK and ERK-responsive signaling, but the JNK activation was less involved. Consistently, oral administration of resveratrol reduced the tissue level of phosphorylated paxillin in the dorsal skin of DNP–HSA-challenged mice. The other tyrosine kinase Tyk2-STAT1 signaling was activated in the dorsal epidermis of antigen-exposed mice, which was associated with allergic inflammation. These results showed that resveratrol inhibited Th2 cytokines- and paxillin-linked allergic responses dependent upon MAPK signaling. Therefore, resveratrol may possess the therapeutic potential of targeting mast cells in preventing the development of allergic inflammation.

Topics: Animals; Cells, Cultured; Cytokines; Dinitrophenols; Disease Models, Animal; Dose-Response Relationship, Drug; Hypersensitivity; Immunoglobulin E; Inflammation; Male; MAP Kinase Signaling System; Mast Cells; Mice; Mice, Inbred BALB C; Molecular Targeted Therapy; Phosphorylation; Phytotherapy; Receptors, IgE; Resveratrol; Serum Albumin; Stilbenes; Th2 Cells

This issue hosts diverse topics, from myeloid derived suppressor cells (MDSC) with their mechanism and role in cancer, the interplay between diet and emerging allergies studied in a genetically closed population, the pleiotropic anti-inflammatory effects of resveratrol, to the quest to achieve more reliable immune correlates of protection against the hepatitis C virus (HCV).

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Hepatitis C; Humans; Hypersensitivity; Immune System; Models, Immunological; Myeloid Cells; Neoplasms; Resveratrol; Stilbenes; Viral Hepatitis Vaccines

Topics: Blastomycosis; Hypersensitivity; Postoperative Complications; Probability; Stilbamidines; Stilbenes

Topics: Anaphylatoxins; Animals; Guinea Pigs; Histamine; Histamine Release; Hypersensitivity; Immune System Diseases; Shock; Stilbenes

Topics: Hypersensitivity; Immune System Diseases; Sporotrichosis; Stilbamidines; Stilbenes

Topics: Anaphylaxis; Aniline Compounds; Head; Head and Neck Neoplasms; Hemangioma; Humans; Hypersensitivity; Neck; Neoplasms; Stilbenes