Dexamethasone alleviate allergic airway inflammation in mice by inhibiting the activation of NLRP3 inflammasome

Dexamethasone (DEX) is the mainstay treatment for asthma, which is a common chronic airway inflammation disease. However, the mechanism of DEX resolute symptoms of asthma is not completely clear. Here, we aimed to analyze the effect of DEX on airway inflammation in OVA-induced mice and whether this effect is related to the inhibition of the activation of NLRP3 inflammasome. Female (C57BL/6) mice were used to establish the allergic airway inflammation model by inhalation OVA. The number of inflammatory cells in the bronchi alveolar lavage fluid (BALF) was counted by Swiss-Giemsa staining, and the contents of IL-1β, IL-18, IL-5 and IL-17 were detected by ELISA. The degree of inflammatory cells infiltration and mucous cells proliferation in lung tissue were separately observed by H&E and PAS staining. The proteins expression of NLRP3, pro-caspase-1, caspase-1, IL-1β, IL-6 and IL-17 in lung tissue were detected by Western blotting. We found that DEX significantly inhibited OVA-induced inflammatory cells infiltration, airway mucus secretion and goblet cell proliferation in mice. The total and classified numbers of inflammatory cells and the levels of IL-1β, IL-18, IL-5 and IL-17 in the BALF of the experimental group were significantly lower than those of the model group after DEX treatment. DEX also significantly inhibited the activity of NLRP3 inflammasome and reduced the protein contents of Pro-Caspase-1, Caspase-1, Capase-1/Pro-Caspase-1, IL-1β, IL-6 and IL-17 in lung tissues. Our study suggested that DEX alleviates allergic airway inflammation by inhibiting the activity of NLRP3 inflammasome and the levels of IL-1β and IL-18.     

Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatment in A/J mice

T cells are sensitive to modulation by cannabinoids as evidenced by their ability to inhibit expression of cytokines, including interleukin (IL)-2 and IL-4. Because T cells play a key role in the pathophysiology of allergic asthma by expressing T helper cell (Th)2 cytokines, the objective of the present studies was to examine the effect of cannabinoids on immunologic and pathologic features associated with the allergic airway response induced by ovalbumin (Ova). A/J mice were systemically sensitized with Ova and subsequently challenged with aerosolized Ova. The steady-state mRNA expression of IL-2 and Th2 cytokines (IL-4, IL-5, and IL-13) was markedly increased in the lungs of Ova-sensitized mice 24 h after a single Ova challenge. Concordantly, the level of total and Ova-specific serum immunoglobulin (Ig)E and intraepithelial mucosubstances in the axial intrapulmonary airway of Ova-sensitized mice was robustly elevated 96 h after the second Ova challenge. Cannabinol (CBN) or Delta(9)-tetrahydrocannabinol (Delta(9)-THC; 50 mg/kg, ip), administered daily for 3 consecutive days before sensitization and then before challenge, significantly attenuated the elevation of IL-2, IL-4, IL-5, and IL-13 steady-state mRNA expression elicited by Ova challenge in the lungs. In addition, the elevation of serum IgE and the mucus overproduction induced by Ova challenge was also markedly attenuated by CBN or Delta(9)-THC administration in Ova-sensitized mice. These results suggest that plant-derived immunomodulatory cannabinoids exhibit potential therapeutic utility in the treatment of allergic airway disease by inhibiting the expression of critical T cell cytokines and the associated inflammatory response.     

Imiquimod, a toll-like receptor 7 ligand, inhibits airway remodelling in a murine model of chronic asthma

1. Imiquimod, a synthetic Toll-like receptor (TLR) 7 ligand, has been shown to attenuate airway inflammation and airway hyperresponsiveness (AHR) in acute murine models of allergic asthma. In the present study, we investigated the effect of imiquimod on allergen-induced airway remodelling in chronic experimental asthma. 2. Ovalbumin (OVA)-sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were exposed to an aerosol of 0.15% imiquimod daily during the period of OVA challenge. Twenty-four hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodelling. The levels of total serum IgE and Th2 cytokines (interleukin (IL)-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) and the expression of transforming growth factor (TGF)-beta1 protein in lungs were measured by ELISA and immunohistochemistry, respectively. 3. The results demonstrated that imiquimod significantly inhibited chronic inflammation, persistent AHR and airway remodelling in chronic experimental asthma. In addition, imiquimod reduced levels of total serum IgE and BALF Th2 cytokines and diminished expression of TGF-beta1 in remodelled airways. 4. In summary, the results of the present study indicate that imiquimod may attenuate the progression of airway inflammation and remodelling, providing potential in the treatment of asthma.     

A carbohydrate fraction, AIP1 from Artemisia iwayomogi suppresses pulmonary eosinophilia and Th2-type cytokine production in an ovalbumin-induced allergic asthma. Down-regulation of TNF-alpha expression in the lung

Asthma is a chronic inflammatory disease of the airways characterized by reversible airway obstruction, airway hyperreactivity, and remodeling of the airways. The incidence of asthma is on the rise despite ongoing intensive asthma research. Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found around Korea and has been used as a traditional anti-inflammatory medicine in liver diseases. We investigated suppressive effects of AIP1, a water-soluble carbohydrate fraction from A. iwayomogi on ovalbumin-induced allergic asthma in BALB/c mice and studied the possible mechanisms of its anti-allergic action. AIP1 significantly reduced pulmonary eosinophilia and Th2 cytokine expression in the lungs as well as serum IgE levels. Flow cytometric analysis of lung-infiltrating cells showed that the surface levels of CD11c and MHC II in CD11c+MHC II+ cells, potent dendritic cells, decreased in animals treated with AIP1. Expression of TNF-alpha, one of several proinflammatory cytokines released into the airway during episodes of asthma, was down-regulated by AIP1 injection, suggesting that reduced expression of TNF-alpha could account for the suppression of pulmonary eosinophilia and Th2-type cytokine production by AIP1.     

Immune mediators in a murine model for occupational asthma: studies with toluene diisocyanate.

Isocyanate-induced asthma, which is the most common type of occupational asthma, has been difficult to diagnose and control, in part, because the biological mechanisms responsible for the disease and the determinants of exposure are not fully defined. To help address these issues, we recently established a murine model of toluene diisocyanate (TDI) asthma using inhalation exposure paradigms consistent with potential workplace exposure. In order to confirm our hypothesis that TDI-induce asthma, like allergic asthma, is predominantly a Th2 response, the ability of mice that were deficient in CD4 or CD8 cells or specific Th1 and Th2 cytokines to develop TDI asthma was examined. The development of allergic asthma was evaluated by monitoring lungs for the presence of eosinophilia, goblet cell metaplasia, epithelial cell alterations, airway hyperreactivity (AHR), and Th2 and Th1 cytokine expression, as well as serum IgE levels and TDI-specific IgG antibodies. Transgenic CD8 or CD4 knockout (KO) mice exhibited significant reductions in AHR, cytokine expression, serum antibody levels, airway inflammation, and histopathological lesions, although in a number of the endpoints the effects were more attenuated in CD4 KO mice. IFNgamma depletion ablated the increase in AHR in TDI-allergic mice, but had only slight to moderate effects on airway histopathology, serum antibody levels, and cytokine expression compared to sensitized/challenged controls. IL-4 and IL-13 deficiency had moderate inhibitory effects, while combined IL-4/IL-13 depletion effectively prevented almost all asthma-associated pathologies. Taken together, these results indicate that TDI asthma, like immune-mediated asthma produced by large-molecular-weight materials, is driven primarily by CD4+ T cells and is dependent upon the expression of Th2 cytokines. However, as with protein-induced asthma models, certain pathologies are influenced by CD8+ T cells and Th1-derived cytokines, such as AHR and cytokine production.     

Anti-interleukin-17 antibodies attenuate airway inflammation in tobacco-smoke-exposed mice

Context: Our previous study showed that the interleukin-17 (IL-17) concentration in lung tissue and in bronchoalveolar lavage fluid (BALF) of rats with tobacco-smoke-induced chronic obstructive pulmonary disease (COPD) was higher than that of control group. However, whether IL-17 inhibitor could decrease the effect of tobacco smoking is not known yet.

Objectives: To investigate the significance of IL-17 antibodies (Ab) in tobacco-smoke-exposed (TSE) mice.

Materials and methods: Male C57/BL6 mice were randomly divided into three groups: TSE group, TSE + anti-IL-17 Ab group, and control group. The number of cells in BALF and the concentrations of IL-17, IL-6, IL-8 and MUC5AC in BALF and lung tissue homogenate were measured. Pulmonary function was measured by pressure sensors, and histologic analysis of the lungs was done in each group.

Results: Lung function tests in TSE + anti-IL-17 Ab group were the same compared with TSE group (P?>?0.05). The total cell count and the number of neutrophil cells in BALF were significantly higher in TSE group than the normal control group (P?<?0.01). Compared with the TSE group, the total cell count in TSE + anti-IL-17 Ab group was decreased, and the percentage of neutrophils in BALF was highly decreased (P?<?0.01). Airway inflammation was alleviated in TSE + anti-IL-17 Ab group by histologic analysis. The concentrations of IL-17 in lung tissue were significantly lower in TSE + anti-IL-17 Ab group than in TSE group (P?<?0.01). IL-17 was mainly expressed in the epithelial cells in the airways of TSE mice. The concentration of IL-6, IL-8 and MUC5AC in BALF was decreased in TSE + anti-IL-17 Ab group compared with TSE group.

Discussion and conclusions: These data support a potential role for IL-17 in airway neutrophilic inflammation in TSE mice. Anti-IL-17 decreased the number of neutrophils as well as the concentration of MUC5AC in the BALF and attenuated neutrophilic airway inflammation.     

Immunomodulatory effects of IL-12 secreted by Lactococcus lactis on Th1/Th2 balance in ovalbumin (OVA)-induced asthma model mice

Asthma is a chronic lung disease characterized by allergen-induced airway inflammation and orchestrated by Th2 cells. Interleukin-12, a Th1-promoting cytokine, is capable of inhibit the Th2-driven allergen-induced airway changes and therefore considered as an attractive molecule to treat asthma. Recent epidemiological and clinical studies suggest a possible role of Lactococcus lactis in the prevention of allergic diseases. In this study, we evaluated the immunomodulatory effects of live L. lactis secreting a biologically active form of IL-12 (LL-IL12) in a mouse model of ovalbumin (OVA)-induced asthma. Intranasal mice administration with LL-IL12 resulted in a shift Th2 to Th1 with elevated IFN-gamma and decreased IL-4 levels. In addition, a profound decrease in airway hyper-responsiveness and pulmonary inflammation was also observed in mice administered with LL-IL12. These promising preclinical results suggest the feasibility of this approach to be used in the treatment of asthma.     

白三烯受体拮抗剂对哮喘小鼠肺组织HMGB1表达的影响

目的 探讨白三烯受体拮抗剂对哮喘小鼠肺组织高迁移率族蛋白B1(HMGB1)表达的影响.方法 72只SPF级Balb/c小鼠随机分为哮喘组(A组)、孟鲁司特治疗组(B组)和生理盐水对照组(C组),每组24只.建守哮喘模型.于第1、2、3、4周4个时段,HE染色观察肺组织病理改变,RT-PCR法检测肺组织HMGB1 mRNA表达,免疫组化标记分析HMGB1在肺组织的分布.结果 HE染色B组肺组织炎症较A组明显减轻.第2周时A、B组肺组织HMGB1的表达明显高于C组[(1.58±0.47)、(1.42士0.30)vs.(0.65±0.15)](P<0.01);B组肺组织HMGB1的表达随治疗时间的延长而减少.结论 白三烯受体拮抗剂能抑制哮喘小鼠气道炎症,减少HMGB1的生成.     

Peroxiredoxin I is a negative regulator of Th2-dominant allergic asthma

Peroxiredoxin (Prx) I, a ubiquitous antioxidant enzyme, is known to protect against inflammation; however, its role in the allergic inflammation remains unidentified. We determined whether intristic Prx I protects against allergic asthma traits using Prx-I knockout (−/−) mice. Prx I (−/−) and wild-type (WT) mice were immunized with ovalbumin (OVA) plus aluminum potassium sulfate (Alum: Th2 adjuvant) and subsequently challenged with OVA. Twenty-four hours after the last OVA challenge, leukocyte influx including eosinophils into bronchoalveolar lavage fluid was significantly greater in Prx I (−/−) mice compared to that in WT mice. On the other hand, when these mice were immunized with OVA + complete Freund's adjuvant (Th1 adjuvant), opposite phenomenon was observed. In the presence of OVA/Alum, peribronchial inflammatory leukocyte infiltration, cholinergic airway resistance, and the lung expression of interleukin (IL)-2 were significantly greater and that of interferon-γ was significantly lesser in Prx I (−/−) than in WT mice. In vitro, OVA/Alum-sensitized Prx I (−/−) T cells proliferated more profoundly than WT T cells when they were cocultured with syngeneic bone marrow-generated dendritic cells. These results indicate that endogenous Prx I protects against allergen-related Th2-type airway inflammation and hyperresponsiveness, at least partly, via the suppression of the lung expression of IL-2 and regulation of the Th1/Th2 balance in addition to its antioxidative properties. Furthermore, Prx I can inhibit allergen-specific T-cell proliferation through immunological synapse. Our findings implicate an alternative therapeutic value of Prx I in the treatment of Th2-skewed allergic airway inflammatory diseases such as atopic asthma.     

Airway inflammation and remodeling of cigarette smoking exposure ovalbumin-induced asthma is alleviated by CpG oligodeoxynucleotides via affecting dendritic cell-mediated Th17 polarization

Cigarette smoking (CS) is common in asthma, aggravating inflammatory reactions. However, the current treatment strategies for asthma are still not effective enough, and novel therapeutic approaches are required for CS-induced asthmatic disorders. We here investigated the ability of CpG oligodeoxynucleotides (CpG-ODNs) to inhibit airway inflammation and remodeling in ovalbumin (OVA)-associated asthma in mice exposed to chronic CS, revealing potential mechanistic insights. Lung tissue specimens were histologically analyzed. Th1/Th2/Th17 associated cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung specimens were quantitated by ELISA, qRT-PCR and immunoblot. Parameters of bone marrow-derived dendritic cells (BMDCs) functions were evaluated as well. The results showed that BALB/c mice after CS and OVA treatments developed an asthmatic phenotype with airway inflammation involving both eosinophils and neutrophils, goblet cell metaplasia, airway remodeling, and elevated OVA-specific serum IgE, serum IL-17A, and BALF Th17/Th2 associated cytokines. CpG-ODNs and budesonide were found to synergistically inhibit inflammatory cell recruitment in the lung, airway remodeling, IgE synthesis, and Th17/Th2 associated cytokines. Mechanistically, CpG-ODNs and budesonide acted synergistically on BMDCs via downregulation of TSLP receptor (TSLPR) and IL-23 production, and subsequently contributed to dampen Th17/Th2 polarization in CS-associated asthma. In conclusion, combined administration of CpG-ODNs and budesonide, in a synergistic manner, inhibits airway inflammation, and tissue remodeling mediated by BMDCs by regulating IL-23 secretion and blocking TSLP signaling, which subsequently contribute to alleviate Th17/Th2 imbalance in CS-associated asthma.     

Anti-asthmatic effect of schizandrin on OVA-induced airway inflammation in a murine asthma model

Asthma comprises a triad of reversible airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. Clinical and experimental findings have established eosinophilia as a sign of allergic disorders. In the present investigation, we evaluated the anti-asthmatic effects of schizandrin and its underlying mechanisms in an in vivo murine asthmatic model. To accomplish this, female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and examined for the following typical asthmatic reactions: increased numbers of eosinophils and other inflammatory cells in bronchoalveolar lavage fluid (BALF); production of Th1 cytokines (such as tumor necrosis factor (TNF)-α in BALF); production of Th2 cytokines (such as interleukin IL-4 and IL-5) in BALF; presence of total and OVA-specific immunoglobulins (Ig)E in serum; presence of oxidative stress; hyperplasia of goblet cells in the lung; and marked influx of inflammatory cells into the lung. Our results collectively show that schizandrin exerts profound inhibitory effects on accumulation of eosinophils into the airways and reduces the levels of IL-4, IL-5, IFN-γ, and TNF-α in BALF. Additionally, schizandrin suppresses the production of reactive oxygen species (ROS) in a dose-dependent manner, and inhibits goblet cell hyperplasia and inflammatory cell infiltration in lung tissue. Thus, schizandrin has anti-asthmatic effects, which seem to be partially mediated by reduction of oxidative stress and airway inflammation, in a murine allergic asthma model. These results indicate that schizandrin may be an effective novel therapeutic agent for the treatment of allergic asthma.     

Anti-allergic effects of salvianolic acid A and tanshinone IIA from Salvia miltiorrhiza determined using in vivo and in vitro experiments

Salvia miltiorrhiza root has been used in Asian traditional medicine for the treatment of cardiovascular diseases, asthma, and other conditions. Salvianolic acid B from S. miltiorrhiza extracts has been shown to improve airway hyperresponsiveness. We investigated the effects of salvianolic acid A, tanshinone I, and tanshinone IIA from S. miltiorrhiza in allergic asthma by using rat RBL-2H3 mast cells and female Balb/c mice. Antigen-induced degranulation was assessed by measuring β-hexosaminidase activity in vitro. In addition, a murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy of salvianolic acid A and tanshinone IIA. Tanshinone I and tanshinone IIA inhibited antigen-induced degranulation of mast cells, but salvianolic acid A did not. Administration of salvianolic acid A and tanshinone IIA decreased the number of immune cells, particularly eosinophils in allergic asthma-induced mice. Histological studies showed that salvianolic acid A and tanshinone IIA reduced mucin production and inflammation in the lungs. Administration of salvianolic acid A and tanshinone IIA reduced the expression and secretion of Th2 cytokines (IL-4 and IL-13) in the bronchoalveolar lavage fluid and lung tissues of mice with ovalbumin-induced allergic asthma. These findings provide evidence that salvianolic acid A and tanshinone IIA may be potential anti-allergic therapeutics.     

4-CMTB Ameliorates Ovalbumin-Induced Allergic Asthma through FFA2 Activation in Mice

Free fatty acid receptor 2 (FFA2, also known as GPR43), a G-protein-coupled receptor, has been known to recognize short-chain fatty acids and regulate inflammatory responses. FFA2 gene deficiency exacerbated disease states in several models of inflammatory conditions including asthma. However, in vivo efficacy of FFA2 agonists has not been tested in allergic asthma. Thus, we investigated effect of 4-chloro-α-(1-methylethyl)-N-2-thiazoylylbenzeneacetanilide (4-CMTB), a FFA2 agonist, on antigen-induced degranulation in RBL-2H3 cells and ovalbumin-induced allergic asthma in BALB/c mice. Treatment of 4-CMTB inhibited the antigen-induced degranulation concentration-dependently. Administration of 4-CMTB decreased the immune cell numbers in the bronchoalveolar lavage fluid and suppressed the expression of inflammatory Th2 cytokines (IL-4, IL-5, and IL-13) in the lung tissues. Histological studies revealed that 4-CMTB suppressed mucin production and inflammation in the lungs. Thus, results proved that FFA2 functions to suppress allergic asthma, suggesting 4-CMTB activation of FFA2 as a therapeutic tool for allergic asthma.     

Suppressive Effect of Carnosol on Ovalbumin-Induced Allergic Asthma

Asthma is a chronic obstructive lung disease characterized by recurrent episodes of bronchoconstriction and wheezing. Conventional asthma treatment involves the suppression of airway inflammation or improving airway flow. Rosmarinus officialis, also known as rosemary, is a Mediterranean plant that is used for the treatment of inflammatory diseases. Carnosol, a diterpenoid found in rosemary extracts, has been known to exhibit anti-inflammatory, anti-tumor, and anti-oxidant effects. The effect of carnosol on allergic responses has not been tested yet. The effect of carnosol on a murine allergic asthma model were investigated. Carnosol inhibited the degranulation of RBL-2H3 mast cells. Carnosol treatment inhibited the increase in the number of eosinophils in the bronchoalveolar lavage fluids (BALF) of mice treated with ovalbumin. Carnosol treatment also inhibited inflammatory responses and mucin production in histologic studies. Carnosol treatment inhibited the increases of IL-4 and IL-13 cytokines expression in both BALF and the lungs. These results suggest that carnosol may have a potential for allergic asthma therapy.     

Salidroside suppresses group 2 innate lymphoid cell-mediated allergic airway inflammation by targeting IL-33/ST2 axis

Salidroside, an active component extracted from Rhodiola rosea, has been reported to inhibit allergic asthma. However, its mechanism has not been fully elucidated. Group 2 innate lymphoid cells (ILC2s) accumulate in the lung and cooperate with other cells to drive type 2 inflammation stimulated by inhaled allergens. The study aims to explore the suppressive effect of salidroside on ILC2s and IL-33/IL-33R (ST2) axis in allergic airway inflammation. The ovalbumin (OVA)-sensitized/challenged mice were established. Airway eosinophil recruitment, increased total IgE in the serum and type 2 cytokines IL-4, IL-5, and IL-13 in the bronchoalveolar lavage fluids and lung tissues were identified in the OVA-induced mice model, all of which were inhibited by pretreatment with different doses of salidroside. Moreover, salidroside suppressed lung total ILC2 and ST2-expressing ILC2 accumulation, lung IL-33 and ST2 expressions in mice. In vitro, OVA could induce IL-33 expression in BEAS-2B cells, which was also effectively inhibited by salidroside. This study firstly reveals salidroside as a potential therapeutic drug for allergic asthma by inhibiting ILC2-mediated airway inflammation via targeting IL-33/ST2 axis.     

Administration of mycobacterial Ag85A and IL-17A fusion protein attenuates airway inflammation in a murine model of asthma

Interleukin (IL)-17A contributes to the development of asthma, especially in severe asthma which has characteristic neutrophil infiltration in airways. However, IL-17A-blocking antibody could escalate T helper (Th) 2 cytokines, such as IL-13, IL-4 in murine models. We aimed at determining the effect of mycobacterial Ag85A and IL-17A fusion protein—Ag85A-IL-17A on airway inflammation in a murine model of asthma. IL-17A recombinant protein fused mycobacterial immunodominant antigen Ag85A was constructed, expressed and purified. The fusion protein was then administrated into BALB/c mice and its anti-inflammatory effects in the infiltration of inflammatory cells, Th2/Th17 cytokines in BALF, histopathological changes of lung tissues as well as chemokines in lung tissues were evaluated in the murine model of asthma. We found that administration of mycobacterial Ag85A and IL-17A fusion protein induced IL-17A specific immunoglobulin (Ig)G in sera and significantly decreased IL-17A and IL-6 levels in bronchoalveolar lavage fluid (BALF). Ag85A-IL-17A vaccinated mice also showed marked reduction in the infiltration of inflammatory cells in peribronchiolar region and significant decrease in total cells, eosinophil cells and neutrophil cells in BALF. The increased levels of IL-13 and IL-4 in BALF of ovalbumin-sensitized mice were significantly reduced by the administration of Ag85A-IL-17A. Furthermore, CD3⁺CD4⁺IL-13⁺ splenocytes stimulated with OVA and CXCL1 mRNA, CCL2 mRNA and GATA-3 mRNA expressed in lung tissues were decreased markedly in Ag85A-IL-17A vaccinated group. Our results demonstrate remarkable antiallergic effects of Ag85A-IL-17A in a murine model of asthma and it may have protective effects on allergic asthma.     

Ligustrazine attenuates inflammation and the associated chemokines and receptors in ovalbumine-induced mouse asthma model

Ligustrazine which is isolated from Chinese herb ligusticum chuanxiong hort, has been widely used in traditional Chinese medicine (TCM) for asthma treatment. In this study, we aim to observe the effect of ligustrazine on inflammation and the associated chemokines and receptors in ovalbumin (OVA)-induced mouse asthma model. Our data demonstrates that ligustrazine suppresses airway hyperresponsiveness to methacholine and lung inflammation in OVA-induced mouse asthma model. Ligustrazine also induces inhibition of inflammatory cells including neutrophils, lymphocytes and eosinophils. In addition, ligustrazine significantly reduces IL-4, IL-5, IL-17A, CCL3, CCL19 and CCL21 level in BALF of asthma mice. Furthermore, ligustrazine induces down-regulation of CCL19 receptor CCR7, STAT3 and p38 MAPK protein expression. Collectively, these results suggest that ligustrazine is effective in attenuation of allergic airway inflammatory changes and related chemokines and receptors in OVA-induced asthma model, and this action might be associated with inhibition of STAT3 and p38 MAPK pathway, which indicates that ligustrazine may be used as a potential therapeutic method to treat asthma.     

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.