calcimycin and Rhinitis--Allergic

Tripterine (TRI), an active monomer in Tripterygium wilfordii, has significant pharmacological activities, such as anti-inflammatory, immunosuppressive and anti-tumor activities. TRI may be used to treat allergic diseases because of its characteristics of immunosuppression.. This study aims to explore the anti-allergic effect of TRI.. It was tested in vivo and in vitro in this study.. The results showed that TRI could significantly inhibit histamine release from rat peritoneal mast cells; the inhibitory effect of TRI on histamine release was stronger than that of other known histamine inhibitors such as disodium cromoglyceride. TRI also significantly inhibited systemic anaphylactic shock induced by compound 48/80 and skin allergy induced by IgE, and inhibited the expression of inflammatory factors secreted by Human Mast Cells (HMC-1) induced by Phorbol 12-Myristate 13- Acetate (PMA) and calcium carrier A23187. In the animal model of allergic rhinitis induced by Ovalbumin (OA), the scores of friction, histamine, IgE, inflammatory factors and inflammatory cells decreased after TRI was administered orally or nasally.. TRI, as an active immunoregulatory factor, has great potential in the treatment of mast cell-mediated allergic diseases.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Calcimycin; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Histamine Release; Humans; Male; Mast Cells; Mice, Inbred BALB C; NF-kappa B; p-Methoxy-N-methylphenethylamine; Pentacyclic Triterpenes; Rats; Rhinitis, Allergic; Tetradecanoylphorbol Acetate; Triterpenes

Allergic inflammation is the foundation of allergic rhinitis and asthma. Although microRNAs are implicated in the pathogenesis of various diseases, information regarding the functional role of microRNAs in allergic diseases is limited. Herein, we reported that microRNA-302e (miR-302e) serves as an important regulator of allergic inflammation in human mast cell line, HMC-1 cells. Our results showed that miR-302e is the dominant member of miR-302 family expressed in HMC-1 cells. Moreover, the expression of miR-302e was significantly decreased in response to phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 or ovalbumin (OVA) stimulation. Overexpression of miR-302e blocked PMA/A23187 or OVA induced the increase in inflammatory cytokines levels, such as IL-1β, IL-6, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin, while miR-302 inhibition further promoted the release of these cytokines. Mechanistically, we found that miR-302e is a novel miRNA that targets RelA, a gene known to be involved in regulating inflammation, through binding to the 3'-UTR of RelA mRNA. Ectopic miR-302e remarkably suppressed the luciferase activity and expression of RelA, whereas down-regulation of miR-302e increased RelA luciferase activity and expression. Pharmacological inhibition of NF-κB reversed the augmented effect of miR-302e down-regulation on inflammatory cytokines level. Taken together, the present study demonstrates miR-302e limits allergic inflammation through inhibition of NF-κB activation, suggesting miR-302e may play an anti-inflammatory role in allergic diseases and function as a novel therapeutic target for the treatment of these diseases.

Topics: Calcimycin; Cell Line; Gene Expression Regulation; Humans; Inflammation; Mast Cells; MicroRNAs; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Tetradecanoylphorbol Acetate; Transcription Factor RelA

Geraniol is a monoterpene alcohol that has anti-fungal, anti-cancer and anti-nociceptive properties, but its anti-allergic rhinitis (AR) property is unclear.. In this study, the anti-inflammatory role and its possible mechanisms of geraniol in human mast cell line (HMC-1) cells stimulated by inflammatory trigger phorbol 12-myristate 13-acetate plus A23187 (PMACI), as well as in ovalbumin (OVA)-induced AR mice models were investigated.. PMACI results in a significant increase in the production of proinflammatory cytokines, such as TNF-α, IL-1β, MCP-1, IL-6 and as well as histamine. Geraniol was found to inhibit both TNF-α, IL-1β and IL-6 protein and mRNA expressions at concentrations of 40, 80, 160 μM. In OVA-induced AR models, geraniol treatment was able to suppress AR biomarkers (OVA-specific IgE and IL-1β as well as histamine) and nasal rub scores. Interestingly, p38, a member of the mitogen-activated protein kinase (MAPK) signaling family, was found to be increasingly hypophosphorylated as geraniol dose was increased. Similar decreases in the nuclear level of p65, a member of the nuclear factor kappa B (NF-κB) signaling pathway, were also observed.. Our data highlights that the anti-inflammatory properties of geraniol on AR-related markers in activated HCM-1 cells and OVA-induced AR models may be mediated through the regulation of the MAPK/NF-κB signaling pathway.

Topics: Acyclic Monoterpenes; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Calcimycin; Cell Line; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Histamine; Humans; Inflammation Mediators; Mice; Mice, Inbred BALB C; Molecular Structure; Ovalbumin; Rhinitis, Allergic; Structure-Activity Relationship; Terpenes; Tetradecanoylphorbol Acetate

Bamboo salt (BS) is a Korean traditional type of salt and has been reported to have therapeutic effects on allergic inflammation. Thymic stromal lymphopoietin (TSLP) aggravates inflammation in the pathogenesis of allergic reactions, such as allergic rhinitis (AR). To confirm an active compound of BS, we investigated the effect of sulfur, a compound of BS, on the levels of TSLP in a human mast cell line, HMC-1 cells and a mouse model of AR using hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaSH). We treated NaSH or BS in HMC-1 cells and activated the HMC-1 cells with phorbol myristate acetate and calcium ionophore A23187 (PMACI). ELISA for the production measurement of TSLP, PCR for the mRNA expression measurement of TSLP, and western blot analysis for the expression measurement of upstream mediators were performed. Mice were treated with NaSH and sensitized with ovalbumin (OVA). The levels of TSLP were measured in serum and nasal mucosa tissue in an OVA-induced AR mouse model. NaSH or BS diminished the production and mRNA expression of TSLP as well as interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the PMACI-activated HMC-1 cells. NaSH or BS diminished the level of intracellular calcium in the PMACI-activated HMC-1 cells. NaSH or BS reduced the expression and activity of caspase-1 in the PMACI-activated HMC-1 cells. And NaSH or BS inhibited the expression of receptor interacting protein-2 and the phosphorylation of extracellular signal-regulated kinase in the PMACI-activated HMC-1 cells. The translocation of NF-κB into the nucleus as well as the phosphorylation and degradation of IκBα in the cytoplasm were diminished by NaSH or BS in the PMACI-activated HMC-1 cells. Furthermore, NaSH inhibited the production of TSLP, IL-6, and IL-8 in TNF-α-activated HMC-1 cells. Finally, the administration of NaSH showed a decrease in number of rubs on mice with OVA-induced AR. And the levels of immunoglobulin E and TSLP in the serum and the level of TSLP in the nasal mucosa tissue of the OVA-induced AR mice were reduced by NaSH. In conclusion, these findings show that H2S, as an active compound of BS is a potential agent to cure allergic inflammation.

Topics: Active Transport, Cell Nucleus; Animals; Calcimycin; Calcium; Caspase 1; Cell Line; Cytokines; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Hydrogen Sulfide; I-kappa B Proteins; Immunoglobulin E; Interleukin-6; Interleukin-8; Mast Cells; Medicine, Korean Traditional; Mice; Mice, Inbred BALB C; NF-kappa B; NF-KappaB Inhibitor alpha; Ovalbumin; Phosphorylation; Real-Time Polymerase Chain Reaction; Receptor-Interacting Protein Serine-Threonine Kinase 2; Rhinitis, Allergic; RNA, Messenger; Sulfides; Tetradecanoylphorbol Acetate; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha

Xinqin, a polyherbal medicine, is an important traditional Chinese herbal formula used in traditional oriental medicine for treatment of allergic rhinitis (AR). The formula is based on the Chinese Pharmacopoeia AIM OF THE STUDY: Previously, Xinqin exhibited potent anti-allergic effect in a guinea pig model of AR. In this study, we explored the molecular mechanism of the anti-allergic effect mediated by Xinqin.. AR was induced in guinea pigs (Hartley) with toluene-2, 4-diisocyanate (TDI) in vivo and in HMC-1 mast cells with A23187/phorbol 12-myristate-13-acetate (PMA) in vitro. The releases of allergic inflammatory mediators such as histamine, leukotriene (LT) D4, immunoglobulin (Ig) E, TNF-α, and IL-6 were analyzed for allergy. The mast cell degranulation was displayed in HMC-1 mast cells. The activities of janus protein kinase 2 (JAK2), signal transduction and activator of transcription 5 (STAT5) and suppressor of cytokine signaling 3 (SOCS3) were evaluated by Western blot.. Treatment with Xinqin resulted in AR symptoms and decreases in levels of histamine, LTD4, IgE, TNF-α, and IL-6 in serum of guinea pig model of AR and in A23187/PMA-stimulated HMC-1 mast cells. Treatment with Xinqin also inhibited cell degranulation in A23187/PMA-stimulated HMC-1 mast cells. The JAK2/STAT5 signaling pathway could play an important role in the anti-allergic activity mediated by Xinqin.. Xinqin exerts the anti-allergic effect by modulating mast cell-mediated allergic responses by down-regulating JAK2/STAT5 signaling pathway. Results from this study provide a mechanistic basis for the application of Xinqin in the treatment of AR.

Topics: Animals; Anti-Allergic Agents; Calcimycin; Cell Degranulation; Cell Line; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Drugs, Chinese Herbal; Guinea Pigs; Histamine; Humans; Immunoglobulin E; Interleukin-6; Janus Kinase 2; Leukotriene D4; Male; Mast Cells; Phosphorylation; Rhinitis, Allergic; Signal Transduction; STAT5 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Tetradecanoylphorbol Acetate; Toluene 2,4-Diisocyanate; Tumor Necrosis Factor-alpha

The antiallergic effects of traditional medicines have long been studied. Traditional Korean medicine, Citrus sunki and bamboo salt, has been used for the treatment of allergic diseases in Korea. K-ALL, composed of Citrus sunki and bamboo salt, is a newly prepared prescription for allergic patients. To develop the new antiallergic agent, we examined the effects of K-ALL through in vivo and in vitro models. K-ALL and naringin (an active compound of K-ALL) significantly inhibited histamine release from rat peritoneal mast cells. This inhibitory effect of K-ALL on histamine release was higher than effects from other known histamine inhibitors such as bamboo salt, Citrus sunki or disodium cromoglycate. K-ALL significantly inhibited systemic anaphylactic shock induced by the compound 48/80 and passive cutaneous anaphylaxis induced by the IgE. K-ALL also inhibited production and mRNA expression of inflammatory cytokines induced by phorbol 12-myristate 13-acetate and the calcium ionophore A23187 on HMC-1 cells (a human mast cell line). In the ovalbumin-induced allergic rhinitis animal model, rub scores, histamine, IgE, inflammatory cytokines and inflammatory cell counts were all reduced by the oral or nasal administration of K-ALL (pre and posttreatment). These results indicate the great potential of K-ALL as an active immune modulator for the treatment of mast cell-mediated allergic diseases.

Topics: Administration, Intranasal; Administration, Oral; Anaphylaxis; Animals; Calcimycin; Calcium Ionophores; Carcinogens; Cell Line; Citrus; Cytokines; Disease Models, Animal; Gene Expression Regulation; Humans; Inflammation Mediators; Male; Mast Cells; Medicine, Korean Traditional; Mice; Mice, Inbred ICR; Plant Extracts; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Tetradecanoylphorbol Acetate