Anti-allergic activity of a Kampo (Japanese herbal) medicine "Sho-seiryu-to (Xiao-Qing-Long-Tang)" on airway inflammation in a mouse model

Effects of a Kampo (Japanese herbal) medicine "Sho-seiryu-to (SST, Xiao-Qing-Long-Tang in Chinese)", which has been used for the treatment of allergic bronchial asthma clinically, were examined on ovalbumin (OVA)-sensitized allergic airway inflammation model (i.e., bronchial asthma) in a mouse. When SST was orally administered at 0.5 g/kg/day from day 1 to 6 days after OVA inhalation, SST reduced the OVA-specific IgE antibody titer in bronchoalveolar lavage (BAL) fluids at 7 days after the OVA inhalation. CD4(+) T cells obtained from the mouse lung produced more interleukin (IL)-4 and IL-5 but less interferon (IFN)-gamma than T cells from nonsensitized control animals. However, oral administration of SST reduced the production of IL-4 and IL-5 and the production of IFN-gamma returned to the control level. In addition, the IL-4 level was increased in the BAL fluid of the OVA-sensitized animals compared to the nonsensitized control, while the IFN-gamma levels decreased. SST reduced the IL-4 levels in the BAL fluids and returned the IFN-gamma level to control levels. Nerve growth factor (NGF) was increased in the BAL fluids of the OVA-sensitized mice over that of nonsensitized mice, but oral administration of SST augmented the NGF levels to approximately 2 times higher than in the sensitized mice. Although lung cells obtained from sensitized mice produced higher levels of NGF than nonsensitized mice, oral administration of SST augmented the production of NGF by the lung cells even higher ( approximately 2 times more than cells from sensitized mice). Administration of anti-NGF antibody to the airway blocked the effects of SST. These results suggest that SST modulates Th1/Th2 balance in the lungs and augmentation of NGF in the lungs may be related to the effects of SST. Pinellic acid (9S, 12S, 13S-trihydroxy-10E-octadecenoic acid), one component of the herbs of SST [Int. Immunopharmacol. 2 (2002) 1183], was purified from the tuber of Pinellia ternata Breitenbach. Oral administration of pinellic acid (50 microg/kg/day) also reduced the OVA-specific IgE antibody titer in BAL fluids from the sensitized mouse. This result suggests that pinellic acid is one of active ingredient(s) in SST.     

Modulation of ovalbumin-induced Th2 responses by second-generation immunomodulatory oligonucleotides in mice

Oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG DNAs) prevent development of T-helper type 2 (Th2) immune responses and reverse established allergic responses in mouse models. We recently reported that second-generation immunomodulatory oligonucleotides (IMOs) containing novel structures (immunomers) and a synthetic immunostimulatory CpR (R=2'-deoxy-7-deazguanosine) motif induce the production of distinct cytokine secretion profiles in vitro and in vivo. In the present study, we evaluated IMOs containing CpG and CpR motifs to modulate allergen-induced Th2 immune responses in prevention and treatment models. Mice sensitized and challenged with ovalbumin (OVA) were treated with a CpG DNA or an IMO by administration either at the time of OVA sensitization (co-administration; prevention) or after establishment of an allergic response (treatment). Spleens, blood, and lungs were collected and analyzed for immune responses. Spleen-cell cultures harvested from OVA-sensitized mice showed a significant decrease in Th2 cytokine levels with a concomitant increase in Th1 cytokine levels only when CpG DNA or IMOs were co-administered with OVA. The co-administration of CpG DNA or IMOs during OVA sensitization significantly reduced serum OVA-specific and total IgE levels in mice. The mice who received CpG DNA or IMOs co-administered with OVA showed a small reduction in serum OVA-specific and total IgG1 levels and a significant increase in serum OVA-specific and total IgG2a levels. Similar results were found in mice with established allergic responses who received IMO treatment. IMO treatment also resulted in strong inhibition of inflammatory cell infiltration and goblet cell hyperplasia in the lungs compared with untreated mice lungs. These data demonstrate that IMOs prevent antigen-induced Th2 immune responses when co-administered to mice during OVA sensitization and that IMOs reverse established allergic responses induced by OVA.     

Airway inflammation and adjuvant effect after repeated airborne exposures to di-(2-ethylhexyl)phthalate and ovalbumin in BALB/c mice

BACKGROUND: Epidemiological studies have suggested an association between exposure to phthalate plasticizers, including di-(2-ethylhexyl)phthalate (DEHP), and increased prevalence of asthma, rhinitis or wheezing. Furthermore, studies in mice have demonstrated an adjuvant effect from DEHP after parenteral administration with the model allergen ovalbumin (OVA). OBJECTIVE: Exposures to DEHP were investigated for adjuvant effects and airway inflammation in a mouse inhalation model. METHODS: BALB/cJ mice were exposed to aerosols of 0.022-13 mg/m(3) DEHP and 0.14 mg/m(3) OVA 5 days/week for 2 weeks and thereafter weekly for 12 weeks. Mice exposed to OVA alone or OVA+Al(OH)(3) served as control groups. Finally, all groups were exposed to a nebulized 1% OVA solution on three consecutive days. Serum, bronchoalveolar lavage (BAL) fluid, and draining lymph nodes were collected 24h later. RESULTS: In the OVA+Al(OH)(3) group, significantly increased levels of OVA-specific IgE and IgG1 in serum as well as of eosinophils in BAL fluid were observed. DEHP affected OVA-specific IgG1 production in a concentration-dependent manner, whereas little effect was seen on IgE and IgG2a. Dose-dependent increases in inflammatory cells were observed in BAL fluids, leading to significantly higher lymphocyte, neutrophil and eosinophil numbers in the OVA+13 mg/m(3) DEHP group. Ex vivo cytokine secretion by cultures of draining lymph nodes suggested that DEHP has a mixed Th1/Th2 cytokine profile. CONCLUSION: Airborne DEHP is able to increase serum IgG1 and lung inflammatory cell levels, but only at very high concentrations. Realistic DEHP levels do not have an adjuvant effect or induce allergic lung inflammation in the present mouse model.     

Oral administration of Bifidobacterium bifidum G9-1 suppresses total and antigen specific immunoglobulin E production in mice

Recent studies have suggested that oral bacteriotherapy with probiotics might be useful in the management of allergic diseases. We investigated the effect of oral administration of Bifidobacterium bifidum G9-1 (BBG9-1) on immunoglobulin (Ig) E production in BALB/c mice. Live BBG9-1 was orally administered to mice for 2 weeks from 1 week before ovalbumin (OVA)-immunization. The treatment of BBG9-1 significantly reduced serum total IgE level. In addition, BBG9-1 significantly and largely reduced the serum level of OVA-specific IgE without lowering of the specific IgG1 and increasing of the specific IgG2a. We also examined T helper type (Th) 1 and Th2 cytokine production from OVA-immunized splenocytes by restimulation with OVA in vitro. Productions of interferon (IFN)-gamma, interleukin (IL)-4 and IL-5 from the splenocytes of mice given BBG9-1 were weaker than those of control mice. We conclude that oral administration of BBG9-1 selectively and powerfully suppresses total and antigen specific IgE production in mice. It is suggested that BBG9-1 is useful for the prophylactic treatment in IgE-dependent allergic diseases.     

Diosgenin, a steroidal sapogenin, enhances antigen-specific IgG2a and interferon-gamma expression in ovalbumin-sensitized BALB/c mice

The effect of diosgenin, the most abundant sapogenin in Chinese yam, on humoral immunity was investigated. Ovalbumin (OVA)-sensitized and challenged BALB/c mice were administered daily with diosgenin for 34 days. The production of OVA-specific serum IgG2a was significantly enhanced by diosgenin treatment, whereas total IgE and OVA-specific IgG1, IgG2a and IgM were unaffected. In parallel with the enhancement of IgG2a, OVA-induced IFN-gamma secretion and mRNA expression were markedly elevated in splenocytes of diosgenin-treated mice, whereas IL-4 expression was unaltered. Furthermore, the expression of T-bet, but not of GATA-3, in splenocytes was up-regulated by diosgenin administration. However, diosgenin treatment did not modulate IL-4 mRNA expression and inflammatory cell infiltration in the lung of OVA-sensitized and challenged mice. Collectively, these data suggest that diosgenin regulates the systemic immune response towards the Th1 direction in response to OVA sensitization. The present study provides evidence to show that intake of diosgenin modulates certain aspects of acquired immunity, including the enhancement of antigen-specific IgG2a and IFN-gamma expression, which may be mediated through the up-regulation of Th1 differentiation.     

S-Allyl cysteine reduces eosinophilic airway inflammation and mucus overproduction on ovalbumin-induced allergic asthma model

S-Allyl cysteine (SAC) is an active component in garlic and has various pharmacological effects, such as anti-inflammatory, anti-oxidant, and anti-cancer activities. In this study, we explored the suppressive effects of SAC on allergic airway inflammation induced in an ovalbumin (OVA)-induced asthma mouse model. To induce asthma, BALB/c mice were sensitized to OVA on days 0 and 14 by intraperitoneal injection and exposed to OVA from days 21 to 23 using a nebulizer. SAC was administered to mice by oral gavage at a dose of 10 or 20 mg/kg from days 18 to 23. SAC significantly reduced airway hyperresponsiveness, inflammatory cell counts, and Th2 type cytokines in bronchoalveolar lavage fluid induced by OVA exposure, which was accompanied by reduced serum OVA-specific immunoglobulin E. In histological analysis of the lung tissue, administration of SAC reduced inflammatory cell accumulation into lung tissue and mucus production in airway goblet cells induced by OVA exposure. Additionally, SAC significantly decreased MUC5AC expression and nuclear factor-κB phosphorylation induced by OVA exposure. In summary, SAC effectively suppressed allergic airway inflammation and mucus production in OVA-challenged asthmatic mice. Therefore, SAC shows potential for use in treating allergic asthma.     

Oral sensitization of W/W(v) mice with ovalbumin and possible involvement of the decrease in gammadelta-T cells

Mast-cell-deficient WBB6F1-W/W(v) mice (W/W(v)) and congenic wild-type (+/+) mice were sensitized by oral administration of 0.1 or 1.0 mg ovalbumin (OVA) in the form of gavage every day for 9 weeks, and active systemic anaphylaxis (ASA) was induced by intraperitoneal injection of OVA. Production of OVA-specific IgG1 in response to oral sensitization of the W/W(v) mice was very high, and the production of IL-4, IL-5 and IL-10 by splenocytes re-stimulated with OVA in vitro was increased. These findings suggest that Th2-dominant helper T-cell activation had occurred. By contrast, production of OVA-specific IgG1 was low in +/+ mice, and no significant increase in production of Th2-type cytokines by the splenocytes of +/+ mice was observed. Population analysis in Peyer's patches by flow cytometry revealed that the proportion of the CD11c(+) cell in the W/W(v) mice was slightly increased after antigen stimulation. Analysis of the cell surface markers of intraepithelial lymphocytes (IELs) by flow cytometry showed that the proportion of TCRgammadelta-T cells was extremely lower in the W/W(v) mice, especially in the antigen sensitized group. The proportion of TCRgammadelta-T cells in the splenocytes of W/W(v) mice was also lower than in +/+ mice. Taken together, the above findings indicate that W/W(v) mice seems to be a good model not only for studying the induction mechanism of food allergy but for examining the role of TCRgammadelta-T cells in food-induced hypersensitivity.     

Pinocembrin attenuates allergic airway inflammation via inhibition of NF-κB pathway in mice

Pinocembrin, one of the primary flavonoids in propolis, possesses many biological activities, including anti-inflammation, anti-oxidation and immunoregulation. This study aimed to evaluate whether pinocembrin could attenuate ovalbumin (OVA)-induced allergic airway inflammation in mice and to explore the possible mechanism. BALB/c mice sensitized and challenged with OVA were administered intraperitoneally with pinocembrin. Airway inflammation and airway hyperresponsiveness were examined. T-helper type (Th) 2 cytokines in bronchoalveolar lavage fluid (BALF) and OVA-specific immunoglobulin E (IgE) in serum were determined. The activation of nuclear factor kappa B (NF-κB) p65 were also measured. Our results showed that pinocembrin resulted in significant inhibition of pathophysiological signs of allergic asthma, including increased pulmonary eosinophilia infiltration, mucus hypersecretion and airway hyperresponsiveness (AHR). Treatment with pinocembrin significantly reduced Th2 cytokines interleukin (IL)-4, IL-5 and IL-13 in BALF, and OVA-specific IgE in serum. Moreover, pinocembrin treatment suppressed phosphorylation of inhibitor-κBα (IκBα) and NF-κB subunit p65 activation in lung tissue of OVA-sensitized mice. These data suggest that pinocembrin may inhibit allergic airway inflammation, and providing potential benefits in the treatment of inflammatory disease.     

Effects of gasoline engine emissions on preexisting allergic airway responses in mice

Gasoline-powered vehicle emissions contribute significantly to ambient air pollution. We hypothesized that exposure to gasoline engine emissions (GEE) may exacerbate preexisting allergic airway responses. Male BALB/c mice were sensitized by injection with ovalbumin (OVA) and then received a 10-min aerosolized OVA challenge. Parallel groups were sham-sensitized with saline. Mice were exposed 6 h/day to air (control, C) or GEE containing particulate matter (PM) at low (L), medium (M), or high (H) concentrations, or to the H level with PM removed by filtration (high-filtered, HF). Immediately after GEE exposure mice received another 10-min aerosol OVA challenge (pre-OVA protocol). In a second (post-OVA) protocol, mice were similarly sensitized but only challenged to OVA before air or GEE exposure. Measurements of airway hyperresponsiveness (AHR), bronchoalveolar lavage (BAL), and blood collection were performed approximately 24 h after the last exposure. In both protocols, M, H, and HF GEE exposure significantly decreased BAL neutrophils from nonsensitized mice but had no significant effect on BAL cells from OVA-sensitized mice. In the pre-OVA protocol, GEE exposure increased OVA-specific IgG(1) but had no effect on BAL interleukin (IL)-2, IL-4, IL-13, or interferon (IFN)-gamma in OVA-sensitized mice. Nonsensitized GEE-exposed mice had increased OVA-specific IgG(2a), IgE, and IL-2, but decreased total IgE. In the post-OVA protocol, GEE exposure reduced BAL IL-4, IL-5, and IFN-gamma in nonsensitized mice but had no effect on sensitized mice. These results suggest acute exposure to the gas-vapor phase of GEE suppressed inflammatory cells and cytokines from nonsensitized mice but did not substantially exacerbate allergic responses.     

Inhibitory effect of Platycodi Radix on ovalbumin-induced airway inflammation in a murine model of asthma

Asthma is a chronic inflammatory disease of the airways characterized by an associated increase in airway responsiveness. In this study, we investigated the inhibitory effect of an aqueous extract from the root of Platycodi Radix (Changkil: CK) on airway inflammation in a murine model of asthma. Mice were sensitized and challenged by ovalbumin (OVA) inhalation to induce chronic airway inflammation and airway remodeling. CK markedly decreased the number of infiltrated inflammatory cells and the levels of Th1 and Th2 cytokines and chemokines compared with those in the OVA-induced group. In addition, CK reduced OVA-specific IgE levels in bronchoalveolar lavage (BAL) fluid. Based on lung histopathological studies, inflammatory cell infiltration and mucus hypersecretion were inhibited by CK administration compared to that in the OVA-induced group. Lung weight was reduced after CK administration. Also, increased generation of ROS in BAL fluid, as well as NF-κB nuclear translocation, by inhalation of OVA was diminished by CK. Moreover, CK reduced the OVA-induced upregulation of matrix metalloproteases activity. These findings indicate that oxidative stress may play a crucial role in the pathogenesis of bronchial asthma induced by OVA and that CK may be useful as an adjuvant therapy for the treatment of bronchial asthma.     

Homoegonol attenuates the asthmatic responses induced by ovalbumin challenge

Homoegonol is a lignan derived from styraxlignolide A, which was isolated from Styrax japonica, a medicinal plant widely used for treatment of inflammatory diseases in Korea. We investigated the efficacy of homoegonol for the treatment of allergic asthma using an ovalbumin (OVA)-induced murine asthma model. The mice were sensitized through intraperitoneal injections of OVA on days 0 and 14. On days 21, 22 and 23 after the initial OVA sensitization, the mice were received OVA airway challenge. Homoegonol was administered by oral gavage at a dose of 30 mg/kg 1 h prior to the OVA challenge. The homoegonol-treated mice exhibited reduced inflammatory cell counts and Th2 cytokines in BALF, AHR, and IgE in the serum compared with the OVA-sensitized/challenged mice. The histological analysis of the lung tissue revealed that the administration of homoegonol attenuated the airway inflammation and the mucus overproduction in airway epithelial lesions induced by OVA through a reduction in expression of inducible nitric oxide synthase and matrix metalloproteinase-9. These findings indicate that homoegonol effectively suppresses the asthmatic responses induced by OVA challenge and suggests that homoegonol exhibits potential as therapeutic drug for allergic asthma.     

Effects of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice

The present study was designed to investigate the effect of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice. Mice were immunized subcutaneously at the base of the tail with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0) and were treated daily with oral administration of various doses of rolipram from days 0 to 20. On day 21, production of anti-OVA IgG and proliferative responses to the antigen were determined. Anti-OVA IgG2a and interferon-gamma (IFN-gamma), as indicators of Th1 responses, and anti-OVA IgG1 and interleukin-10 (IL-10), as indicators of Th2 responses, were also measured. The results showed that treatment with rolipram failed to affect the production of OVA-specific IgG but decreased the proliferation of spleen cells to the antigen. Its inhibitory effect on these immune responses was correlated with a marked decrease in IFN-gamma but not IL-10 production, although neither anti-OVA IgG2a nor IgG1 production was affected by rolipram. These results suggest that rolipram may preferentially inhibit Th1 responses more effectively than Th2 responses. Administration of rolipram resulted in suppression of antigen (OVA)-induced arthritis in mice. The suppression of joint inflammation by rolipram was associated with the inhibition of the OVA-specific proliferative responses of spleen cells and IFN-gamma secretion. These results indicate that rolipram may be effective in regulating Th1-mediated diseases such as rheumatoid arthritis.     

Skullcapflavone II attenuates ovalbumin-induced allergic rhinitis through the blocking of Th2 cytokine production and mast cell histamine release

Allergic rhinitis is a common heterogeneous chronic upper airway disorder and is an IgE-mediated inflammation characterized by one or more nasal symptoms such as sneezing, itching, nasal discharge, rhinorrhea, post nasal drainage and nasal blockage. In the present study, the effects of skullcapflavone II (SCFII) on upper airway inflammation, Th2 cytokines, and NF-κB signaling in an ovalbumin (OVA)-induced allergic rhinitis (AR) murine model in vivo were investigated. OVA-induced AR mice increased nasal symptoms, eosinophils and mast cells infiltration into nasal cavity, OVA-specific IgE/IgG1 and histamine in serum, Th2 cytokines including IL-13 and GATA3, and NF-κB signaling in NALF and lung homogenate. Interestingly, treatment of SCFII reduced the levels of OVA-specific IgE/IgG1 and histamine in serum, of Th2 cytokines and of NF-κB signaling in the NALF and the lung homogenate, and histopathological changes in the nasal tissue and the lung. Also, dexamethasone suppressed such increases. The results of this study suggested that SCFII may ameliorate allergic inflammation of upper airway in AR mice model by blocking the Th2 cytokine production, the NF-κB signal pathway and the mast cell histamine release. Taken together, we suggest that SCFII may be used as a therapeutic agent for patients with Th2-mediated or mast cell-mediated allergic diseases.     

Vaccination with an ovalbumin/interleukin-4 fusion DNA efficiently induces Th2 cell-mediated immune responses in an ovalbumin-specific manner

To more effectively drive immune responses toward antigen-specific T helper type 2 (Th2) cellmediated responses, we constructed a mammalian expression vector (pOVA/IL4) carrying a fused gene in which the ovalbumin (OVA) cDNA was covalently linked to murine interleukin-4 (IL-4) cDNA. A biologically active OVA/IL4 protein was expressed by the transfected COS cells with the pOVA/IL4 DNA, as demonstrated by Western blotting and cytokine bioassay. Intramuscular injection of BALB/c mice with the pOVA/IL4 DNA increased both the production of OVA-specific IL-4 by CD4⁺ T cells and the ratio of anti-OVA IgG1 to anti-OVA IgG2a isotypes, while the injection with the pOVA DNA alone, or with the mixture of the pOVA and plL4 DNA did no or little increase. Furthermore, the OVA-specific, Th2 cell-mediated immune responses were significantly enhanced by multiple injections with the pOVA/IL4 DNA. These studies indicate that the direct linkage of an OVA gene to an IL-4 gene in the expression plasmid confines the effects of IL-4 to the OVA-specific cells, efficiently driving the immune response toward OVA-specific., Th2 cell-mediated responses.     

Covalent linkage of IL-12 and ovalbumin confines the effects of IL-12 to ovalbumin-specific immune responses

In order to direct the form of the immune response in an antigen-specific manner, we constructed a fusion protein (OVA/IL12) that contained the T cell-dependent antigen, ovalbumin (OVA), covalently linked to murine interleukin-12 (IL-12). The OVA/IL12 protein was produced in a baculovirus expression system and was purified by anti-OVA immunoaffinity chromatography. The purified OVA/IL12 protein displayed potent IL-12 bioactivity in an IL-12 proliferation assay. BALB/c mice immunized with the OVA/IL12 protein produced increased quantities of anti-OVA IgG2a antibody compared with mice immunized with recombinant OVA alone. Lymph node cells from the immunized mice with the OVA/IL12 protein produced large amounts of IFN-gamma when restimulatedin vitro with OVA, while those from mice immunized with the OVA protein produced little or no IFN-gamma. In contrast, immunization with a mixture of OVA and free recombinant IL-12 also induced IFN-gamma production, which was not OVA-specific. These studies indicate that the OVA/IL12 fusion protein can induce OVA-specific, Th1-dominated imnune responses, and that the covalent linkage of OVA and IL-12 confines the effect of IL-12 to OVA-specific cells.     

The hyperresponsiveness of W/W(v) mice to oral sensitization is associated with a decrease in TCRgammadelta-T cells

We have already reported that WBB6F1-W/W(v) (W/W(v)) mice, which have mutations in the c-kit gene, are highly susceptible to oral sensitization, and that the proportion of TCRgammadelta-T cells among the intraepithelial lymphocytes (IELs) (gammadelta-IELs) of W/W(v) is much lower than in congenic wild-type (+/+) mice. In this study we examined an inhibitory role of gammadelta-IELs in oral sensitization using two different methods. First, wild-type (+/+) mice were sensitized by oral administration of 1.0 mg ovalbumin (OVA) by gavage every day for 9 weeks after anti-TCRgammadelta antibody treatment 4 times. The treatment resulted in an enhanced OVA-specific IgG1 antibody production, active systemic anaphylaxis (ASA), and Th2-dominant cytokine production. Next, W/W(v) mice whose bone marrow cells were reconstituted from C57BL/6J mice for 5 months were sensitized by oral administration of OVA. The OVA-specific IgG1 antibody titer in the bone marrow-reconstituted W/W(v) mice was neither significantly enhanced, nor ASA was induced. The proportion of gammadelta-IELs in the reconstituted mice was much higher than that in the untreated W/W(v) mice. The above findings suggest that the decrease or increase in number of gammadelta-IELs enhances or decreases oral sensitization respectively. These results show that gammadelta-IELs have an important role in the oral tolerance to food antigens.     

Skullcapflavone II inhibits ovalbumin-induced airway inflammation in a mouse model of asthma

Skullcapflavone II is a flavonoid derived from Scutellaria baicalensis, a widely used herbal medicine in anti-inflammatory and anticancer therapy in Korea. Skullcapflavone II antagonized the bradykinin receptor more potently than any of the other flavonoids derived from this plant. Here, we were investigated its therapeutic effects in a mouse model of ovalbumin (OVA)-induced allergic asthma. Administration of skullcapflavone II significantly reduced airway hyperresponsiveness (AHR), airway eosinophilia, Th2 cytokine production, and increased transforming growth factor-β1 (TGF-β1) levels in bronchoalveolarlavage (BAL) fluids and lungs from OVA-sensitized and -challenged mice. Skullcapflavone II administration also significantly suppressed subepithelial collagen deposition and goblet cell hyperplasia, elevated Smad7 expression and suppressed pSmad2/3 levels. Collectively, these findings indicate that skullcapflavone II, a potential bradykinin antagonist, reduced the major pathophysiological features of allergic asthma, at least in part by acting on TGF-β1/Smad signaling pathways. Thus, skullcapflavone II may have therapeutic potential for the treatment of allergic asthma.     

ortho-Phthalaldehyde enhances allergen-specific IgE production without allergen-specific IgG in ovalbumin-sensitized mice

ortho-Phthalaldehyde (OPA) is commonly used as a safer and more effective chemical disinfectant for use with medical devices in hospitals. However, the cases of patients with occupational bronchial asthma or contact dermatitis are recently reported among workers in the medical professions who were exposed to OPA disinfectant. Mechanism of allergic reaction associated with OPA is poorly understood. The purpose of this study is that OPA may act as an immunological adjuvant in the allergic reaction accompanied by enhanced specific-IgE production in response to allergen challenge in OVA-sensitized mice. OPA induced increase of total cell numbers, and reflected infiltration of neutrophils in BAL fluid after allergen challenge in sensitized mice, dose-dependently. However, total protein concentration in BAL fluid did not change in the all of groups. The OPA induced up-regulation of eotaxin and monocyte chemotactic protein-1 mRNAs in the lung as well as the increase in OVA-specific IgE in sensitized mice compared with non-sensitized controlled mice without increase in the level of OVA-specific IgG. Cytokines IL-4 and IL-5 mRNA were expressed by allergen (OVA) challenge in both lungs collected from OPA-administrated-sensitized and OPA-administrated-nonsensitized mice. From these data, we concluded that low concentration of OPA that enhanced the OVA-induced recruitment of neutrophils to the lung and the production of allergen-specific IgE, suggesting that OPA acts as an immunological adjuvant.     

Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation

Thymoquinone (TQ), the main active constituent of the volatile oil extracted from Nigella sativa's seeds, has been reported to have an anti-inflammatory and immune stimulatory effect on bronchial asthma and inflammation. However, little is known about the factors and mechanisms underlying these effects. In the present study, we examined the effect of TQ on airway inflammation in a mouse model of allergic asthma. Intraperitoneal injection of TQ before airway challenge of ovalbumin (OVA)-sensitized mice resulted in a marked decrease in lung eosinophilia and the elevated Th2 cytokines observed after airway challenge with OVA antigen; both in vivo, in the bronchoalveolar lavage (BAL) fluid and in vitro, following stimulation of lung cells with OVA. TQ also decreased the elevated serum levels of OVA-specific IgE and IgG1. Histological examination of lung tissue demonstrated that TQ significantly inhibited allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells. While TQ showed a significant effect in inhibiting IL-4, IL-5 and IL-13 and some effect in inducing IFN-gamma production in the BAL fluid, it did show a slight effect on in vitro production of IL-4 by cultured lung cells stimulated with OVA antigen. These data suggest that TQ attenuates allergic airway inflammation by inhibiting Th2 cytokines and eosinophil infiltration into the airways; thus demonstrating its potential anti-inflammatory role during the allergic response in the lung.