P2Y12 antagonist attenuates eosinophilic inflammation and airway hyperresponsiveness in a mouse model of asthma

Leukotriene E4 (LTE4) that plays a key role in airway inflammation is expressed on platelets and eosinophils. We investigated whether blocking of the P2Y12 receptor can suppress eosinophilic inflammation in a mouse model of asthma because platelets and eosinophils share this receptor to be activated. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by OVA nebulization. On each challenge day, clopidogrel, a P2Y12 antagonist was administered 30 min. before each challenge. Forty‐eight hours after the last OVA challenge, mice were assessed for airway hyperresponsiveness (AHR), cell composition and cytokine levels, including chemokine ligand 5 (CCL5), in bronchoalveolar lavage (BAL) fluid. EOL cells were treated with LTE4, with or without clopidogrel treatment, and intracellular and extracellular eosinophil cationic protein (ECP) expressions were measured to find the inhibiting function of P2Y12 antagonist on eosinophilic activation. The levels of P2Y12 expression were increased markedly in the lung homogenates of OVA‐sensitized and ‐challenged mice after platelet depletion. Administration of clopidogrel decreased AHR and the number of airway inflammatory cells, including eosinophils, in BAL fluid following OVA challenge. These results were associated with decreased levels of Th2 cytokines and CCL5. Histological examination showed that inflammatory cells as well as mucus‐containing goblet cells were reduced in clopidogrel‐administered mice compared to vehicle‐treated mice. Clopidogrel inhibited extracellular ECP secretion after LTE4 stimulation in EOL‐1 cells. Clopidogrel could prevent development of AHR and airway inflammation in a mouse model of asthma. P2Y12 can be a novel therapeutic target to the suppression of eosinophils in asthma.     

CC chemokine receptor-2 is not essential for the development of antigen-induced pulmonary eosinophilia and airway hyperresponsiveness

Monocyte chemoattractant proteins-1 and -5 have been implicated as important mediators of allergic pulmonary inflammation in murine models of asthma. The only identified receptor for these two chemokines to date is the CCR2. To study the role of CCR2 in a murine model of Ag-induced asthma, we compared the pathologic and physiological responses of CCR2(-/-) mice with those of wild-type (WT) littermates following immunization and challenge with OVA. OVA-immunized/OVA-challenged (OVA/OVA) WT and CCR2(-/-) mice developed significant increases in total cells recovered by bronchoalveolar lavage (BAL) compared with their respective OVA-immunized/PBS-challenged (OVA/PBS) control groups. There were no significant differences in BAL cell counts and differentials (i.e., macrophages, PMNs, lymphocytes, and eosinophils) between OVA/OVA WT and CCR2(-/-) mice. Serologic evaluation revealed no significant difference in total IgE and OVA-specific IgE between OVA/OVA WT mice and CCR2(-/-) mice. Lung mRNA expression and BAL cytokine protein levels of IL-4, IL-5, and IFN-gamma were also similar in WT and CCR2(-/-) mice. Finally, OVA/OVA CCR2(-/-) mice developed increased airway hyper-responsiveness to a degree similar to that in WT mice. We conclude that following repeated airway challenges with Ag in sensitized mice, the development of Th2 responses (elevated IgE, pulmonary eosinophilia, and lung cytokine levels of IL-4 and IL5) and the development of airway hyper-responsiveness are not diminished by a deficiency in CCR2.     

黄芩苷通过苦味受体促进哮喘小鼠呼吸道炎性细胞凋亡

全球哮喘患者有3亿多人。目前,约有一半患者的病情不能较好地用现有药物来控制。因此,寻找新的更有效的治疗哮喘病的药物是非常必要的。最近的研究发现,苦味受体(bitter taste receptors,Tas2rs)在呼吸系统中表达,且苦味剂对哮喘有治疗潜力,苦味受体可能成为哮喘治疗的新靶点。为此,本文研究了苦味化合物黄芩苷(baicalin,BA)对哮喘的干预作用,分析黄芩苷对哮喘小鼠呼吸道炎性细胞凋亡的干预作用及其与苦味信号转导的关系。选雄性BALB/c小鼠,随机分为对照组(CK组)、腹腔注射致敏加雾化吸入卵清蛋白(ovalbumin,OVA)激发制成的哮喘模型组(OVA组)和黄芩苷灌胃干预哮喘组(OVA+BA组)。结果发现,OVA组小鼠肺泡灌洗液中白细胞总数和分类细胞计数显著增加,黄芩苷干预组白细胞数量显著减少;HE染色后,OVA组小鼠肺组织中可见炎性细胞浸润、肺泡隔增厚和肺泡囊缩小,上述症状在OVA+BA组小鼠肺部明显减轻;实时荧光定量RT-PCR检测发现,肺组织中黏蛋白Muc5ac表达水平在OVA组明显增高(P <0.05),黄芩苷干预组显著低于OVA组(P <0.05)。OVA致敏哮喘小鼠呼吸道中Tas2r108、Tas2r126、Tas2r135和Tas2r143及其下游信号转导分子α-gust和Trpm5下调表达(P <0.05),促凋亡因子P53、Bax和胱天蛋白酶(caspase,Casp)Casp3转录抑制,凋亡抑制基因Bcl2上调表达,胱天蛋白酶3活性显著降低(P <0.05);黄芩苷干预组4个Tas2rs及苦味信号转导分子转录上调(P <0.05),促凋亡基因P53、Bax和Casp3转录上调,Bcl2转录抑制,胱天蛋白酶3活性显著高于OVA组(P <0.05)。结果表明,黄芩苷干预可激活哮喘鼠呼吸道苦味信号转导通路,并使呼吸道炎性细胞减少、黏蛋白分泌减少。即苦味物质黄芩苷可能作为一种苦味受体激动剂,通过激活苦味信号转导系统促进呼吸道炎性细胞凋亡,减轻肺部炎症和损伤,缓解哮喘发作。     

The effect of apigenin,an aryl hydrocarbon receptor antagonist,in Phthalate-Exacerbated eosinophilic asthma model

Endocrine disrupting chemicals have been known to contribute to the aggravation of inflammatory diseases including asthma. We aimed to investigate the effects of mono-n-butyl phthalate (MnBP) which is one of the representing phthalates, and its antagonist in an eosinophilic asthma mouse model. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) with alum and followed by three nebulized OVA challenges. MnBP was administered through drinking water administration throughout the study period, and its antagonist, apigenin, was orally treated for 14 days before OVA challenges. Mice were assessed for airway hyperresponsiveness (AHR), differential cell count and type 2 cytokines in bronchoalveolar lavage fluid were measured in vivo. The expression of the aryl hydrocarbon receptor was markedly increased when MnBP was administered. MnBP treatment increased AHR, airway inflammatory cells (including eosinophils), and type 2 cytokines following OVA challenge compared to vehicle-treated mice. However, apigenin treatment reduced all asthma features, such as AHR, airway inflammation, type 2 cytokines, and the expression of the aryl hydrocarbon receptor in MnBP-augmented eosinophilic asthma. Our study suggests that MnBP exposure may increase the risk of eosinophilic inflammation, and apigenin treatment may be a potential therapy for asthma exacerbated by endocrine-disrupting chemicals.     

Flt-3 ligand reverses late allergic response and airway hyper-responsiveness in a mouse model of allergic inflammation

Flt3 ligand (Flt3-L) is a growth factor for dendritic cells and induces type 1 T cell responses. We recently reported that Flt3-L prevented OVA-induced allergic airway inflammation and suppressed late allergic response and airway hyper-responsiveness (AHR). In the present study we examined whether Flt3-L reversed allergic airway inflammation in an established model of asthma. BALB/c mice were sensitized and challenged with OVA, and AHR to methacholine was established. Then mice with AHR were randomized and treated with PBS or 6 microg of Flt3-L i.p. for 10 days. Pulmonary functions and AHR to methacholine were examined after rechallenge with OVA. Treatment with Flt3-L of presensitized mice significantly suppressed (p < 0.001) the late allergic response, AHR, bronchoalveolar lavage fluid total cellularity, absolute eosinophil counts, and inflammation in the lung tissue. There was a significant decrease in proinflammatory cytokines (TNF-alpha, IL-4, and IL-5) in bronchoalveolar lavage fluid, with a significant increase in serum IL-12 and a decrease in serum IL-5 levels. There was no significant effect of Flt3-L treatment on serum IL-4 and serum total IgE levels. Sensitization with OVA significantly increased CD11b(+)CD11c(+) cells in the lung, and this phenomenon was not significantly affected by Flt3-L treatment. These data suggest that Flt3-L can reverse allergic airway inflammation and associated changes in pulmonary functions in murine asthma model.     

Immune Modulatory Effects of IL-22 on Allergen-Induced Pulmonary Inflammation

IL-22 is a Th17/Th22 cytokine that is increased in asthma. However, recent animal studies showed controversial findings in the effects of IL-22 in allergic asthma. To determine the role of IL-22 in ovalbumin-induced allergic inflammation we generated inducible lung-specific IL-22 transgenic mice. Transgenic IL-22 expression and signaling activity in the lung were determined. Ovalbumin (OVA)-induced pulmonary inflammation, immune responses, and airway hyperresponsiveness (AHR) were examined and compared between IL-22 transgenic mice and wild type controls. Following doxycycline (Dox) induction, IL-22 protein was readily detected in the large (CC10 promoter) and small (SPC promoter) airway epithelial cells. IL-22 signaling was evidenced by phosphorylated STAT3. After OVA sensitization and challenge, compared to wild type littermates, IL-22 transgenic mice showed decreased eosinophils in the bronchoalveolar lavage (BAL), and in lung tissue, decreased mucus metaplasia in the airways, and reduced AHR. Among the cytokines and chemokines examined, IL-13 levels were reduced in the BAL fluid as well as in lymphocytes from local draining lymph nodes of IL-22 transgenic mice. No effect was seen on the levels of serum total or OVA-specific IgE or IgG. These findings indicate that IL-22 has immune modulatory effects on pulmonary inflammatory responses in allergen-induced asthma.     

Protective Effects of the Polyphenol Sesamin on Allergen-Induced TH2 Responses and Airway Inflammation in Mice

Allergic asthma is a lifelong airway condition that affects people of all ages. In recent decades, asthma prevalence continues to increase globally, with an estimated number of 250,000 annual deaths attributed to the disease. Although inhaled corticosteroids and β-adrenergic receptor agonists are the primary therapeutic avenues that effectively reduce asthma symptoms, profound side effects may occur in patients with long-term treatments. Therefore, development of new therapeutic strategies is needed as alternative or supplement to current asthma treatments. Sesamin is a natural polyphenolic compound with strong anti-oxidative effects. Several studies have reported that sesamin is effective in preventing hypertension, thrombotic tendency, and neuroinflammation. However, it is still unknown whether sesamin can reduce asthma-induced allergic inflammation and airway hyperresponsiveness (AHR). Our study has revealed that sesamin exhibited significant anti-inflammatory effects in ovalbumin (OVA)-induced murine asthma model. We found that treatments with sesamin after OVA sensitization and challenge significantly decreased expression levels of interleukin-4 (IL-4), IL-5, IL-13, and serum IgE. The numbers of total inflammatory cells and eosinophils in BALF were also reduced in the sesamin-treated animals. Histological results demonstrated that sesamin attenuated OVA-induced eosinophil infiltration, airway goblet cell hyperplasia, mucus occlusion, and MUC5AC expression in the lung tissue. Mice administered with sesamin showed limited increases in AHR compared with mice receiving vehicle after OVA challenge. OVA increased phosphorylation levels of IκB-α and nuclear expression levels of NF-κB, both of which were reversed by sesamin treatments. These data indicate that sesamin is effective in treating allergic asthma responses induced by OVA in mice.     

Dual TCR expression biases lung inflammation in DO11.10 transgenic mice and promotes neutrophilia via microbiota-induced Th17 differentiation

A commonly used mouse model of asthma is based on i.p. sensitization to OVA together with aluminum hydroxide (alum). In wild-type BALB/c mice, subsequent aerosol challenge using this protein generates an eosinophilic inflammation associated with Th2 cytokine expression. By constrast, in DO11.10 mice, which are transgenic for an OVA-specific TCR, the same treatment fails to induce eosinophilia, but instead promotes lung neutrophilia. In this study, we show that this neutrophilic infiltration results from increased IL-17A and IL-17F production, whereas the eosinophilic response could be restored upon blockade of IFN-γ, independently of the Th17 response. In addition, we identified a CD4(+) cell population specifically present in DO11.10 mice that mediates the same inflammatory response upon transfer into RAG2(-/-) mice. This population contained a significant proportion of cells expressing an additional endogenous TCR α-chain and was not present in RAG2(-/-) DO11.10 mice, suggesting dual antigenic specificities. This particular cell population expressed markers of memory cells, secreted high levels of IL-17A, and other cytokines after short-term restimulation in vitro, and triggered a neutrophilic response in vivo upon OVA aerosol challenge. The relative numbers of these dual TCR lymphocytes increased with the age of the animals, and IL-17 production was abolished if mice were treated with large-spectrum antibiotics, suggesting that their differentiation depends on foreign Ags provided by gut microflora. Taken together, our data indicate that dual TCR expression biases the OVA-specific response in DO11.10 mice by inhibiting eosinophilic responses via IFN-γ and promoting a neutrophilic inflammation via microbiota-induced Th17 differentiation.     

Lycopene suppresses ovalbumin-induced airway inflammation in a murine model of asthma

In this study, we attempt to determine whether lycopene regulates inflammatory mediators in the ovalbumin (OVA)-induced murine asthma model. To address this, mice were sensitized and challenged with OVA, and then treated with lycopene before the last OVA challenge. Administration of lycopene significantly alleviated the OVA-induced airway hyperresponsiveness to inhaled methacholine. Administration of lycopene also resulted in a significant inhibition of the infiltration of inflammatory immunocytes into the bronchoalveolar lavage, and attenuated the gelatinolytic activity of matrix metalloproteinase-9 and the expression of eosinophil peroxidase. Additionally, lycopene reduced the increased levels of GATA-3 mRNA level and IL-4 expression in OVA-challenged mice. However, it increased T-bet mRNA level and IFN-γ expression in lycopene-challenged mice. These findings provide new insight into the immunopharmacological role of lycopene in terms of its effects in a murine model of asthma.     

IL-33 induces Th17-mediated airway inflammation via mast cells in ovalbumin-challenged mice

Allergic asthma is characterized by infiltration of eosinophils, elevated Th2 cytokine levels, airway hyperresponsiveness, and IgE. In addition to eosinophils, mast cells, and basophils, a variety of cytokines are also involved in the development of allergic asthma. The pivotal role of eosinophils in the progression of the disease has been a subject of controversy. To determine the role of eosinophils in the progression of airway inflammation, we sensitized and challenged BALB/c wild-type (WT) mice and eosinophil-deficient ΔdblGATA mice with ovalbumin (OVA) and analyzed different aspects of inflammation. We observed increased eosinophil levels and a Th2-dominant response in OVA-challenged WT mice. In contrast, eosinophil-deficient ΔdblGATA mice displayed an increased proportion of mast cells and a Th17-biased response following OVA inhalation. Notably, the levels of IL-33, an important cytokine responsible for Th2 immune deviation, were not different between WT and eosinophil-deficient mice. We also demonstrated that mast cells induced Th17-differentiation via IL-33/ST2 stimulation in vitro. These results indicate that eosinophils are not essential for the development of allergic asthma and that mast cells can skew the immune reaction predominantly toward Th17 responses via IL-33 stimulation.     

Increased lungkine and chitinase levels in allergic airway inflammation: a proteomics approach

Asthma is a chronic inflammatory disease characterized by pulmonary eosinophilia and airway hyperresponsiveness. Mechanisms underlying the pathogenesis of asthma are still not fully understood. The present study investigated alterations in global protein expression in bronchoalveolar lavage fluid in allergic airway inflammation using a proteomics approach. BALB/c mice sensitized and challenged with ovalbumin developed airway eosinophilia, mucus hypersecretion, elevation of immunoglobulin E, and airway hyperresponsiveness. Lavage fluid proteins from normal and asthmatic mice were resolved by two-dimensional gel electrophoresis, and identified by peptide mass fingerprinting matrix-assisted laser desorption/ionization-time of flight mass spectrometry. A total of 28 protein spots were significantly altered. Several of these proteins were undetectable or at very low levels in normal mice but were significantly increased in airway inflammation. These include lungkine, a recently described chemokine, a family of chitinases including Ym1, Ym2, and acidic mammalian chitinase, gob-5, a protein that mediates mucus secretion, and surfactant protein-D, a C-type lectin capable of modulating inflammatory responses. Overall, proteomics is a powerful tool in unraveling protein expression changes in allergic airway inflammation. The proteins identified in this study may be associated with the pathogenesis of allergic airway inflammation and may also be found useful as surrogate biomarkers for asthma.     

Acinetobacter baumannii infection inhibits airway eosinophilia and lung pathology in a mouse model of allergic asthma

Allergic asthma is a dysregulation of the immune system which leads to the development of Th2 responses to innocuous antigens (allergens). Some infections and microbial components can re-direct the immune response toward the Th1 response, or induce regulatory T cells to suppress the Th2 response, thereby inhibiting the development of allergic asthma. Since Acinetobacter baumannii infection can modulate lung cellular and cytokine responses, we studied the effect of A. baumannii in modulating airway eosinophilia in a mouse model of allergic asthma. Ovalbumin (OVA)-sensitized mice were treated with live A. baumannii or phosphate buffered saline (PBS), then intranasally challenged with OVA. Compared to PBS, A. baumannii treatment significantly reduced pulmonary Th2 cytokine and chemokine responses to OVA challenge. More importantly, the airway inflammation in A. baumannii-treated mice was strongly suppressed, as seen by the significant reduction of the proportion and the total number of eosinophils in the bronchoalveolar lavage fluid. In addition, A. baumannii-treated mice diminished lung mucus overproduction and pathology. However, A. baumannii treatment did not significantly alter systemic immune responses to OVA. Serum OVA-specific IgE, IgG1 and IgG2a levels were comparable between A. baumannii- and PBS-treated mice, and tracheobronchial lymph node cells from both treatment groups produced similar levels of Th1 and Th2 cytokines in response to in vitro OVA stimulation. Moreover, it appears that TLR-4 and IFN-γ were not directly involved in the A. baumannii-induced suppression of airway eosinophilia. Our results suggest that A. baumannii inhibits allergic airway inflammation by direct suppression of local pulmonary Th2 cytokine responses to the allergen.     

淫羊藿苷对RSV感染诱发哮喘小鼠体内PGD2水平的影响

摘要 目的：观察淫羊藿苷对RSV感染诱发哮喘小鼠血清及支气管肺泡灌洗液中前列腺素D2（Prostaglandin D2,PGD2）表达水平的影响,以期为哮喘治疗寻找新的靶点。方法：30只Balb/c小鼠随机均分为三组：即正常组,OVA/RSV-YYH组（即淫羊藿苷治疗组）及OVA/RSV-非YYH组（即未经淫羊藿苷治疗组）。卵蛋白致敏RSV感染诱发小鼠哮喘模型成功建立后,予以淫羊藿苷2.5 mg连续腹腔注射治疗2周,比较治疗前后肺功能检测结果、支气管肺泡灌洗液（bronchoalveolar lavage fluid,BALF）中细胞分类计数、血清及BALF中PGD2表达水平、肺组织病理学变化。结果：淫羊藿苷治疗后,哮喘小鼠肺功能较治疗前明显改善,差异有统计学意义（P<0.05）;PGD2水平较前明显下降,差异有统计学意义（P<0.05）;各分类白细胞计数较前明显减少,差异有统计学意义（P<0.01）,气道管壁增厚及管腔狭窄现象较前明显改善,肺组织炎症细胞浸润较前减少。结论：淫羊藿苷可有效降低RSV感染诱发哮喘小鼠体内炎性介质PGD2水平,从而改善气道重塑,减轻小鼠的哮喘症状,它可能是以后哮喘治疗的一个新的靶点。     

STAT3小分子抑制剂FLLL31对卵白蛋白致敏小鼠气道炎症治疗活性的初步研究

目的:研究新结构化合物FLLL31抑制卵白蛋白(OVA)致敏引发的小鼠气道炎症的活性,探讨FLLL31治疗哮喘的初步疗效。方法:雄性BALB/c小鼠(18~20 g)随机分为4组,每组10只,包括正常对照组(Control组)、模型对照组(OVA组)、地塞米松组(1 mg/kg,腹腔注射)和FLLL31组(15 mg/kg,口服灌胃)。各组小鼠分别于第0 d和第14 d致敏,每只鼠腹腔注射20μg OVA和2.25 mg Al(OH)3凝胶,FLLL31自致敏第24 d开始给药,给药周期为7 d;于第28、29、30 d以气管滴入OVA进行攻击,攻击前1 h给予受试化合物FLLL31及阳性药地塞米松。结果:小鼠肺灌流液炎症细胞分类计数、肺组织病理分析等实验结果证明,FLLL31以15 mg/kg连续给药7 d后,与模型组相比,抑制了小鼠肺部气道中炎症细胞的浸润,明显改善OVA致敏引发的小鼠气道炎症症状;ELISA结果证明FLLL31降低小鼠肺灌流液中炎症因子白细胞介素6的含量;免疫组化结果显示FLLL31降低OVA致敏小鼠肺部白细胞介素6受体浓度,减少中性粒细胞标志物淋巴细胞抗原6G(Ly6G)的表达(P0.05)。结论:特异抑制STAT3的新结构化合物FLLL31在体内对OVA致敏小鼠模型气道炎症有较好的改善和免疫调节活性。     

黄芩苷通过增强抗氧化和抑制细胞凋亡减轻哮喘小鼠雄性生殖损伤

生殖健康是人口与健康领域的重要议题。作为全球最常见的呼吸道疾病哮喘会影响男性生殖功能,但相关机制鲜有报道。本文研究了黄酮类化合物黄芩苷(baicalin, BA)对哮喘小鼠睾丸损伤的干预作用及相关机制。选择雄性BALB/c小鼠随机分为对照组(CK组)、卵清蛋白(ovalbumin, OVA)致敏的哮喘组(OVA组)和黄芩苷干预哮喘组(OVA+BA组)。结果发现,3组小鼠体重无明显差异。OVA组小鼠睾丸系数和精子数量显著降低(P<0.05),精子畸形率显著增加(P<0.05);黄芩苷干预组小鼠睾丸系数显著增加(P<0.05),精子畸形率显著降低(P<0.05)。HE染色观察到OVA组小鼠睾丸组织生精小管结构损伤,精子发生异常,生精细胞减少,Johnson得分显著降低;BA干预组生精小管直径及生精上皮细胞高度显著增加,生精小管基膜结构较完整,Johnson得分显著提高(P<0.05);试剂盒法检测氧化还原指标发现,OVA组睾丸组织过氧化氢(H₂O₂)和丙二醛(MDA)含量显著增加(P<0.05),总超氧化物歧化...     

A novel human anti‐VCAM‐1 monoclonal antibody ameliorates airway inflammation and remodelling

Asthma is a chronic inflammatory disease induced by Type 2 helper T cells and eosinophils. Vascular cell adhesion molecule‐1 (VCAM‐1) has been implicated in recruiting eosinophils and lymphocytes to pathological sites in asthma as a regulatory receptor. Accordingly, monoclonal antibody (mAb) against VCAM‐1 may attenuate allergic inflammation and pathophysiological features of asthma. We attempted to evaluate whether a recently developed human anti‐VCAM‐1 mAb can inhibit the pathophysiological features of asthma in a murine asthma model induced by ovalbumin (OVA). Leucocyte adhesion inhibition assay was performed to evaluate the in vitro blocking activity of human anti‐VCAM‐1 mAb. OVA‐sensitized BALB/c mice were treated with human anti‐VCAM‐1 mAb or isotype control Ab before intranasal OVA challenge. We evaluated airway hyperresponsiveness (AHR) and bronchoalveolar lavage fluid analysis, measured inflammatory cytokines and examined histopathological features. The human anti‐VCAM‐1 mAb bound to human and mouse VCAM‐1 molecules and inhibited adhesion of human leucocytes in vitro. AHR and inflammatory cell counts in bronchoalveolar lavage fluid were reduced in mice treated with human anti‐VCAM‐1 mAb as compared with a control Ab. The levels of interleukin (IL)‐5 and IL‐13, as well as transforming growth factor‐β, in lung tissue were decreased in treated mice. Human anti‐VCAM‐1 mAb reduced goblet cell hyperplasia and peribronchial fibrosis. In vivo VCAM‐1 expression decreased in the treated group. In conclusion, human anti‐VCAM‐1 mAb attenuated allergic inflammation and the pathophysiological features of asthma in OVA‐induced murine asthma model. The results suggested that human anti‐VCAM‐1 mAb could potentially be used as an additional anti‐asthma therapeutic medicine.     

咪喹莫特对慢性哮喘模型小鼠肺组织中基质金属蛋白酶-9-表达的影响

目的：观察Toll样受体7配体咪喹莫特对慢性哮喘小鼠模型气道重塑及肺组织中基质金属蛋白酶MMP-9表达的影响。方法：36只BALB／c小鼠按随机原则分成正常对照组、哮喘模型组、咪喹莫特组,每组12只。通过卵蛋白致敏,气道激发8周,末次激发24h后,检测各组小鼠气道反应性,HE染色观察气道炎症变化;Masson三色染色观察气道纤维化的改变;real-timePCR和western—blot分别检测肺组织中MMP-9的mRNA和蛋白表达。结果：慢性哮喘组小鼠气道炎症、气道高反应性和气道重塑较正常对照小鼠明显加重,而咪喹莫特组小鼠模型的气道炎症和气道反应性及气道重塑均较哮喘模型组小鼠减少或降低。慢性哮喘组小鼠肺组织MMP-9的mRNA和蛋白水平均较正常对照小鼠明显增加（P〈0．05）,而咪喹莫特治疗可显著降低哮喘小鼠肺组织MMP-9的mRNA和蛋白水平（P〈0．05）。结论：咪喹莫特能够显著抑制慢性哮喘小鼠模型的气道炎症、降低气道高反应性并减轻气道重塑,这可能与其抑制MMP-9的表达有关。     

A comparative study of toxocariasis and allergic asthma in murine models

Histopathology of the lung and total IgE in serum were compared in toxocariasis and allergic asthma murine models using BALB/c and C57BL/6 mice. Infection with Toxocara canis resulted in both strains of mice in marked histological changes and increased levels of total serum IgE. The ovalbumin (OVA) sensitization/challenge treatment for the induction of allergic asthma resulted in similar histological changes in BALB/c and, to a less extent, in C57BL/6 mice. Serum IgE levels of OVA-treated C57BL/6 mice were low. Histological changes observed included perivascular infiltration with eosinophils and mononuclear cells, peribronchiolitis, alveolitis and mucus production. Although these changes in addition to increased IgE production did occur in T. canis-infected C57BL/6 mice they were more pronounced in BALB/c mice. Thus, BALB/c mice appear to be the most appropriate strain of mice to perform studies on the possible connection between infection with T. canis and allergic asthma.