Influenza virus-induced dendritic cell maturation is associated with the induction of strong T cell immunity to a coadministered,normally nonimmunogenic protein

We evaluated the proposal that during microbial infection, dendritic cells (DCs) undergo maturation and present a mixture of peptides derived from the microbe as well as harmless environmental antigens. Mice were exposed to an aerosol of endotoxin free ovalbumin (OVA) in the absence or presence of influenza virus. In its absence, OVA failed to induce B and T cell responses and even tolerized, but with influenza, OVA-specific antibodies and CD8+ cytolytic T lymphocytes developed. With or without infection, OVA was presented selectively in the draining mediastinal lymph nodes, as assessed by the comparable proliferation of infused, CD8+ and CD4+, TCR transgenic T cells. In the absence of influenza, these OVA-specific T cells produced little IL-2, IL-4, IL-10, and IFN-gamma, but with infection, both CD4+ and CD8+ T cells made high levels of IL-2 and IFN-gamma. The OVA plus influenza-treated mice also showed accelerated recovery to a challenge with recombinant vaccinia OVA virus. CD11c+ DCs from the mediastinal lymph nodes of infected mice selectively stimulated both OVA- and influenza-specific T cells and underwent maturation, with higher levels of MHC class II, CD80, and CD86 molecules. The relatively slow (2-3 d) kinetics of maturation correlated closely to the time at which OVA inhalation elicited specific antibodies. Therefore respiratory infection can induce DC maturation and simultaneously B and T cell immunity to an innocuous antigen inhaled concurrently.     

Anti-asthmatic effects of Angelica dahurica against ovalbumin-induced airway inflammation via upregulation of heme oxygenase-1

Asthma is a chronic immune inflammatory disease characterized by variable airflow obstruction. The present study was undertaken to assess the effects of an Angelica dahurica Bentham et Hooker ethanolic extract (AD) on airway inflammation in an ovalbumin (OVA)-induced airway inflammation model. Mice that received AD displayed significantly lower airway eosinophilia, cytokine levels, including interleukin (IL)-4, IL-5, and tumor necrosis factor (TNF)-alpha levels, mucus production and immunoglobulin (Ig)E, compared with OVA-induced mice. In our experiments, AD treatment reduced airway inflammation and suppressed oxidative stress in the OVA-induced asthma model, partly via induction of heme oxygenase (HO)-1. The effects of AD on OVA-induced HO-1 induction were partially reversed by the HO-1 inhibitor, tin protoporphyrin (SnPP). Our results clearly indicate that AD is a suppressor of airway allergic inflammation, and may thus be effectively used as an anti-inflammatory drug in the treatment of asthma.     

建立支气管哮喘大鼠模型的新方法及评价

目的 探讨建立支气管哮喘动物模型的新方法.方法 20只清洁级SD大鼠随机分为哮喘组和对照组,每组10只,哮喘组以小剂量卵蛋白(OVA)1 mg致敏并激发为大鼠哮喘模型,对照组以氢氧化铝凝胶致敏,以0.9％氯化钠溶液激发.观察2组大鼠肺组织病理、支气管肺泡灌洗液(BALF)细胞分类及血清OVA-specific IgE水...     

纳气平喘颗粒对大鼠哮喘肺组织病理变化影响探讨

目的探讨纳气平喘颗粒对哮喘大鼠呼吸道病理学变化的影响及其对肺水代谢的药理作用。方法采用卵清蛋白(Ovalbumin,OVA)致敏方法建立支气管哮喘大鼠模型。Wistar大鼠69只随机分为正常对照组、哮喘模型组、纳气平喘颗粒干预组、地塞米松干预组。观察和比较各组大鼠肺内各段气道的病理学变化,测定肺组织湿干重比值(Wet Dry ratio,W/D),并进行炎性细胞和杯状细胞计数。结果哮喘模型组与正常对照组相比,哮喘模型组呼吸道管腔狭窄,腔内有大量黏液栓(Mucous Plug)形成;黏膜上皮受损、气道平滑肌增厚、黏膜水肿(Muco-sal Edema)及炎性细胞浸润等病理学变化显著。地塞米松干预组及纳气平喘颗粒干预组上述病理学变化减轻;纳气平喘颗粒组肺组织W/D值、炎性细胞和杯状细胞数值均低于哮喘模型组,差异有统计学意义(P<0.05)。结论纳气平喘颗粒药理作用与地塞米松相似,能够有效地改善哮喘大鼠呼吸道病理学变化,对哮喘引起的黏液高分泌及黏膜水肿有一定的调节作用。     

Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: role of CB1/CB2 receptors

The endocannabinoid system (ECS) consists of two cannabinoid (CB) receptors, namely CB₁ and CB₂ receptor, and their endogenous (endocannabinoids) and exogenous (cannabinoids, e.g. delta-9-tetrahydrocannabinol (THC)) ligands which bind to these receptors. Based on studies suggesting a role of THC and the ECS in inflammation, the objective of this study was to examine their involvement in type I hypersensitivity using a murine model of allergic airway inflammation. THC treatment of C57BL/6 wildtype mice dramatically reduced airway inflammation as determined by significantly reduced total cell counts in bronchoalveolar lavage (BAL). These effects were greatest when mice were treated during both, the sensitization and the challenge phase. Furthermore, systemic immune responses were significantly suppressed in mice which received THC during sensitization phase. To investigate a role of CB_1/2 receptors in this setting, we used pharmacological blockade of CB₁ and/or CB₂ receptors by the selective antagonists and moreover CB₁/CB₂ receptor double-knockout mice (CB₁^−/−/CB₂^−/−) and found neither significant changes in the cell patterns in BAL nor in immunoglobulin levels as compared to wildtype mice. Our results indicate that the activation of the ECS by applying the agonist THC is involved in the development of type I allergies. However, CB₁/CB₂ receptor-independent signalling seems likely in the observed results.     

Potential allergenicity research of Cry1C protein from genetically modified rice

With the development of genetically modified crops, there has been a growing interest in available approaches to assess the potential allergenicity of novel gene products. We were not sure whether Cry1C could induce allergy. We examined the protein with three other proteins to determine the potential allergenicity of Cry1C protein from genetically modified rice. Female Brown Norway (BN) rats received 0.1 mg peanut agglutinin (PNA), 1 mg potato acid phosphatase (PAP), 1 mg ovalbumin (OVA) or 5 mg purified Cry1C protein dissolved in 1 mL water by daily gavage for 42 days to test potential allergenicity. Ten days after the last gavage, rats were orally challenged with antigens, and physiologic and immunologic responses were studied. In contrast to sensitization with PNA, PAP and OVA Cry1C protein did not induce antigen-specific IgG2a in BN rats. Cytokine expression, serum IgE and histamine levels and the number of eosinophils and mast cells in the blood of Cry1C group rats were comparable to the control group rats, which were treated with water alone. As Cry1C did not show any allergenicity, we make the following conclusion that the protein could be safety used in rice or other plants.     

Allergic immune-regulatory effects of Adlay Bran on an OVA-immunized mice allergic model

Allergy is an inflammation associated with an elevated T helper (Th) 2 lymphocyte responses to allergens and elevated serum IgE levels and cytokines. In one of our previous studies using a cell model, various flavonoids were found to be involved the anti-inflammatory effects of adlay bran. The present study investigated the effect of the ethyl-acetate fraction of ethanolic extract of adlay bran (ABE-EtOAc) in an ovalbumin (OVA)-immunized murine model. Six-week-old female BALB/c mice underwent OVA sensitization and were used as an allergy model. An orogastric gavage was used to force feed these mice with 240 mg/kg ABE-EtOAc from their sixth week through their twelfth week. Immune reactions were determined by measuring changes in Th2-type cytokine (IL-4 and IL-5) levels and production of antibodies. ABE-EtOAc was found capable of regulating the Th1/Th2 immune reaction through its regulation of IL-2 and IL-4. It also significantly reduced the production of anti-OVA IgE antibodies (10%), increased the secretion of IFN-γ and decreased the secretion of IL-6 (38%). These results suggest that adlay bran extract can reduce an allergic reaction by balancing Th1/Th2 immune responses and that it might be used in the treatment of this condition.     

Panax ginseng ameliorates airway inflammation in an ovalbumin-sensitized mouse allergic asthma model

Ethnopharmacological relevance

Panax ginseng (PG) is a medicinal herb that has been used to treat various immune diseases including asthma and COPD. In this study, we investigated the inhibitory mechanism of PG on asthma parameters in mice.

Materials and methods

BALB/c mice were sensitized with 20 μg/200 μl OVA adsorbed on 1.0 mg/50 μl aluminum hydroxide gel adjuvant by i.p. injection on days 0 and 14. Mice were then challenged with 5% OVA in PBS to the nose for 30 min once a day for 3 days, from day 20 until day 22, using a nebulizer. PG (20 mg/kg) or vehicle was administrated by i.p. injection once a day 10 min before every OVA challenge for 3 days. The recruitment of inflammatory cells into bronchoalveolar lavage fluid or lung tissues was measured. The expression of EMBP, Muc5ac, CD40, and CD40 ligand (CD40L) in lung tissues was investigated. In addition, the cytokines and mitogen activated protein (MAP) kinases were measured by RT-PCR and Western blot.

Results and conclusions

PG restored the expression of EMBP, Muc5ac, CD40, and CD40L, as well as the mRNA and protein levels of interleukin (IL)-1β, IL-4, IL-5, and tumor necrosis factor (TNF)-α. In addition, PG inhibited the numbers of goblet cells and further small G proteins and MAP kinases in bronchoalveolar lavage cells and lung tissues increased in ovalbumin-induced allergic asthma in mice. These results suggest that PG may be used as a therapeutic agent in asthma, based on reductions of various allergic responses.