Immunomodulatory effect of Quercetin on dysregulated Th1/Th2 cytokine balance in mice with both type 1 diabetes and allergic asthma

T-helper subtype imbalance is intricate in type 1 diabetes (T1D) and asthma initiation. The role of quercetin in immunedysregulation in comorbid conditions of T1D and asthma is not available. In this study, it was thought worthy toevaluate the role of quercetin on modulating Th1/Th2 cytokine dysregulation in comorbid diabetic asthma. Male Balb/cmice were injected intravenously with alloxan (80 mg/kg) to persuade T1D. Succeeding diabetes introduction, twointraperitoneal sensitizing doses of ovalbumin emulsion (50 µg ovalbumin blended with 2.5 mg alum/sensitization) weregiven on days 3 and 8. Mice were given intranasal challenges of ovalbumin (100 µg ovalbumin/25 µl of sterile saline) ondays 13–15. Oral quercetin treatment (10–30 mg/kg) was given daily on days 3–15. Nasal hyperresponsiveness (NHR)was recorded immediately after Ova challenge on day 16. Bronchoalveolar lavage fluid (BALF), blood, and lungs werecollected 1-hour post NHR for further analysis. Quercetin treatment significantly decreased eosinophils, interleukin-4while increasing interferon-gamma in blood, and BALF and reduced the allergic airway inflammation by inhibitinginflammatory cell infiltration and mucous cell metaplasia. Furthermore, quercetin with a dose of 30 mg/kg demonstrateda significant glucose reduction. Thus, quercetin exerted dose-dependent anti-asthma activity by modulating Th1/Th2balance with glucose-lowering potential in comorbid mice.

Prenatal mold exposure is associated with development of atopic dermatitis in infants through allergic inflammation / Exposição pré-natal a mofo está associada ao desenvolvimento de dermatite atópicaem neonatos por reação alérgica

Abstract Objective Mold exposure in early life may be associated with development of atopic dermatitis; however, studies of this link are inconclusive and evidence for the underlying mechanism(s) is lacking. This study identified the association between the time of mold exposure and development of atopic dermatitis and investigated the underlying mechanisms. Method The association between atopic dermatitis and mold exposure was examined in the Cohort for Childhood Origin of Asthma and Allergic Diseases birth cohort study (n = 1446). Atopic dermatitis was diagnosed at 1 year of age by pediatric allergists. Exposure to mold was assessed by questionnaire. The Illumina MiSeq platform was used to examine the environmental mycobiome in 20 randomly selected healthy infants and 20 infants with atopic dermatitis at 36 weeks of gestation. Results Prenatal, but not postnatal, mold exposure was significantly associated with atopic dermatitis (adjusted odds ratio, 1.36; 95% confidence interval, 1.01-1.83). Levels of total serum IgE at 1 year of age were higher in infants with atopic dermatitis exposed to mold during pregnancy than in healthy infants not exposed to mold during pregnancy (p = 0.021). The relative abundance of uncultured Ascomycota was higher in infants with atopic dermatitis than in healthy infants. The relative abundance of uncultured Ascomycota correlated with total serum IgE levels at 1 year of age (r = 0.613, p < 0.001). Conclusion Indoor mold exposure during the fetal period is associated with development of atopic dermatitis via IgE-mediated allergic inflammation. Avoidance of mold exposure during this critical period might prevent the development of atopic dermatitis.

Resumo Objetivo A exposição ao mofo no início da vida pode estar associada ao desenvolvimento de dermatite atópica; contudo, os estudos sobre esse vínculo são inconclusivos e faltam evidências dos mecanismos subjacentes. Identificamos a associação entre o momento da exposição ao mofo e o desenvolvimento de dermatite atópica e investigamos os mecanismos subjacentes. Método A associação entre dermatite atópica e exposição a mofo foi examinada em um estudo de coorte de nascimento da Origem da Asma e de Doenças Alérgicas em Crianças (COCOA) (n = 1446). A dermatite atópica foi diagnosticada em pacientes com um ano de vida por pediatras alergistas. A exposição ao mofo foi avaliada por um questionário. A plataforma Illumina MiSeq foi utilizada para examinar o microbioma ambiental em 20 neonatos saudáveis escolhidos aleatoriamente e 20 com dermatite atópica a 36 semanas de gestação. Resultados A exposição pré-natal, porém não pós-natal, ao mofo foi significativamente associada à dermatite atópica (razão de chances ajustada, 1,36; intervalo de confiança de 95%, 1,01-1,83). Os níveis séricos totais de Imunoglobulina E (IgE) no primeiro ano de vida foram maiores em neonatos com dermatite atópica expostos a mofo durante a gravidez do que em neonatos não expostos a mofo durante a gravidez (p = 0,021). A abundância relativa de Ascomycota não cultivado foi maior em neonatos com dermatite atópica do que em neonatos saudáveis. A abundância relativa de Ascomycota não cultivado correlacionou-se com os níveis séricos totais de IgE no primeiro ano de vida (r = 0,613, p < 0,001). Conclusão A exposição ao mofo no ambiente domiciliar durante a gravidez está associada ao desenvolvimento de dermatite atópica por meio de reação alérgica mediada por IgE. A prevenção à exposição ao mofo durante o período crítico da gravidez pode prevenir o desenvolvimento de dermatite atópica.

Chinese medicine Yu-Ping-Feng-San attenuates allergic inflammation by regulating epithelial derived pro-allergic cytokines / 中国天然药物

This study aimed to investigate the mechanisms of Yu-Ping-Feng-San (YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis (AD). AD mouse model was established with fluorescein isothiocyanate (FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells (DCs) and group 2 innate lymphoid cells (ILC2s) were detected by flow cytometry. Human immortalized keratinocyte (HaCaT) cells were stimulated with Poly(I:C)/TNF-α in vitro to assessthymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and nuclear factor-κB (NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay (ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.

Effects of Alcohol Extracts of Bark and Male Flower of Eucommia ulmoides Oliv. on Airway Allergic Inflammation of Model Mice / 中国中医药信息杂志

Objective To investigate the effects of alcohol extract of bark and male flower of Eucommia ulmoides Oliv. on airway allergic inflammation induced by chicken ovalbumin (OVA) in mice; To explore its mechanism of action. Methods On day 0, day 7, mice were intraperitoneally injected OVA for sensitization, followed by nasal stimulation for 21 days to establish airway allergic inflammation mice models. The mice were divided into normal group, model group, alcohol extract of bark of Eucommia ulmoides Oliv. group, alcohol extract of male flower of Eucommia ulmoides Oliv.group,and Dexamethasone group.Each medication group was given relevant medicine for gavage. The lung tissue was embedded in HE and PAS dyeing, to observe the pathological changes of bronchus and surrounding lung. The levels of serum OVA-IgE, IL-4, IFN-γ and IL-13 were measured by ELISA. The expression of ICAM-1, VEGF, MMP9 and TIMP1 were detected by immunohistochemistry. Flow cytometry was used to detect the expression of Th17 cells in peripheral blood. The expressions of TNF-α and IL-6 mRNA in lung tissue were detected by RT-PCR. Results The model group showed changes of airway allergic inflammatory such as eosinophils and other inflammatory cell infiltration, bronchial spasm, and mucus secretion. Lung histopathology in alcohol extract of bark and male flower of Eucommia ulmoides Oliv.groups was improved significantly(P<0.05).Compared with the normal group, the levels of serum OVA-IgE, IL-4 and IL-13 increased in model group, while the level of IFN-γ decreased (P<0.05, P<0.01). The expressions of ICAM-1, VEGF and MMP9 increased, while the expression of TIMP1 decreased (P<0.01); peripheral blood IL-17+cells increased (P<0.01); the expressions of TNF-α and IL-6 mRNA increased. Compared with the model group, the levels of serum OVA-IgE, IL-4 and IL-13 decreased in alcohol extract of bark and male flower of Eucommia ulmoides Oliv. groups (P<0.05, P<0.01); the expressions of ICAM-1 and VEGF decreased (P<0.05, P<0.01); the expression of TIMP1 increased. Alcohol extract of bark and male flower of Eucommia ulmoides Oliv.could down-regulate IL-17+cells,reduce the expression of IL-6 mRNA(P<0.05,P<0.01). Alcohol extract of bark of Eucommia ulmoides Oliv. group could induce the secretion of IFN-γ (P<0.01), and down-regulate the expression of TNF-α mRNA(P<0.05).Alcohol extract of male flower of Eucommia ulmoides Oliv. group could significantly down-regulate the expression of MMP9 (P<0.05). Conclusion Alcohol extract of bark and male flower of Eucommia ulmoides Oliv.can induce the production of OVA-IgE,inhibit secretion of Th2 cytokines, inhibit the expression of adhesion molecules, depress Th17 cells, so as to inhibit the airway allergic inflammation.

Airway Dysbacteriosis Exacerbated Murine Airway Allergic Inflammation / 中山大学学报(医学科学版)

[Objective] To investigate the effects of airway dysbacteriosis on the development of murine atlergic airway diseases (AAD).[Methods] Female C57BL/6 mice were neubulized with Vancomycin for 10 days and then were sacrificed.The bacterial population in bronchoalveolar lavage fluid (BALF) were evaluated using 16S rRNA high-throughput sequencing technology,exploriug the method of establishing an airway dysbacteriosis mouse model.After the mouse model was established successfully,airway dysbacteriosis mouse models were established by the same method,and based on that,the mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation.The frequency of nasal rubbing behaviors per mice was counted;the total cell number and eosinophil relative abundance in BALF were evaluated;the lung tissue inflammation and goblet cell metaplasia were assessed according to histopathological features;and the IgE level in serum,IFN-γ,IL-4 and IL-5 levels in BALF,and IL-33 levels in serum,BALF and intestine tissue were measured by ELISA.[Results] Nebulization of Vancomycin increased Bradyrhizobium,Sphingopyxis,Cupriavidus,Pelomonas,and decreased Akkermansia and Prevotella_6 in airway,inducing significant airway dysbacteriosis.Using the animal model,further study found that airway dysbacteriosis exacerbated OVA-induced airway allergic inflammation,including increased nasal rubbing frequency,higher serun IgE level,more total cell count especially eosinophil infiltration,more serious lung tissue inflammation and goblet cell metaplasia.Additionally,compared to OVA group,mice in Dysbacteriosis and OVA group had significantly increased level of Th2 cytokine IL-4 and IL-5,and significantly decreased Thl cytokine IFN-γin BALF,which revealed that mice in Dysbacteriosis and OVA group had mote remarkable Thl/Th2 imbalance.Furthermore,IL-33 level showed a significant increase in BALF,but didn't change in serum or intestine tissue in Dysbacteriosis and OVA group compared to OVA group.Indicating that airway dysbacteriosis may only affect the local production of IL-33.[Conclusions] An airway dysbacteriosis mouse model was established by Vancomycin nebulization successfully.Airway dysbacteriosis may activate innate lymphoid cells (ILC) and Th2 cell by inducing local IL-33 secreting,which leads to the imbalance of Th1/Th2,and in turn promotes the development of AAD.

Regulation of Th2 Cell Immunity by Dendritic Cells

Th2 cell immunity is required for host defense against helminths, but it is detrimental in allergic diseases in humans. Unlike Th1 cell and Th17 cell subsets, the mechanism by which dendritic cells modulate Th2 cell responses has been obscure, in part because of the inability of dendritic cells to provide IL-4, which is indispensable for Th2 cell lineage commitment. In this regard, immune cells other than dendritic cells, such as basophils and innate lymphoid cells, have been suggested as Th2 cell inducers. More recently, multiple independent researchers have shown that specialized subsets of dendritic cells mediate Th2 cell responses. This review will discuss the current understanding related to the regulation of Th2 cell responses by dendritic cells and other immune cells.

STAT6 and PARP Family Members in the Development of T Cell-dependent Allergic Inflammation

Allergic inflammation requires the orchestration of altered gene expression in the target tissue and in the infiltrating immune cells. The transcription factor STAT6 is critical in activating cytokine gene expression and cytokine signaling both in the immune cells and in target tissue cells including airway epithelia, keratinocytes and esophageal epithelial cells. STAT6 is activated by the cytokines IL-4 and IL-13 to mediate the pathogenesis of allergic disorders such as asthma, atopic dermatitis, food allergy and eosinophilic esophagitis (EoE). In this review, we summarize the role of STAT6 in allergic diseases, its interaction with the co-factor PARP14 and the molecular mechanisms by which STAT6 and PARP14 regulate gene transcription.

Phellinus linteus Extract Exerts Anti-asthmatic Effects by Suppressing NF-kappaB and p38 MAPK Activity in an OVA-induced Mouse Model of Asthma

Phellinus linteus has been used as a traditional herbal medicine in Asian countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, the protective effects of P. linteus against experimental asthma have not been fully investigated. The objective of this study was to determine whether P. linteus ethanol extract (PLE) suppresses inflammatory response in an OVA-induced asthma model. As expected, the oral administration of PLE significantly inhibited eosinophilic airway inflammation and airway hyperresponsiveness in OVA-challenged BALB/c mice. Supporting these data, the augmentation of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in lung tissues and bronchoalveolar lavage fluid after OVA inhalation was markedly attenuated by PLE. Furthermore, PLE reduced OVA-induced activation of NF-kappaB and p38 MAPK in lung tissues. Therefore, our results suggest the potential of P. linteus as a therapeutic agent for asthma.

Ribes fasciculatum var. chinense Attenuated Allergic Inflammation In Vivo and In Vitro

Ribes fasciculatum var. chinense MAX. (R. fasciculatum) has traditionally been used in Korea to treat inflammatory diseases. However, the exact mechanism that accounts for the anti-inflammatory effect of R. fasciculatum is not completely understood. We aimed to ascertain the pharmacological effects of R. fasciculatum on both compound 48/80- or histamine-induced scratching behaviors and 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of R. fasciculatum, we evaluated the effects of R. fasciculatum on the production of inflammatory mediators in LPS-stimulated macrophage cells. Treatment of R. fasciculatum significantly reduced compound 48/80- or histamine-induced the pruritus in mice. R. fasciculatum attenuated the AD symptoms such as eczematous, erythema and dryness and serum IgE levels in AD model. Additionally, R. fasciculatum inhibited the production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The maximal rates of TNF-alpha and IL-6 inhibition by R. fasciculatum (1 mg/ml) were approximately 32.12% and 46.24%, respectively. We also showed that R. fasciculatum inhibited the activation of nuclear factor-kappa B in LPS-stimulated macrophages. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of R. fasciculatum as a potential molecule for use in the treatment of allergic inflammatory diseases.

A Novel Synthetic Mycolic Acid Inhibits Bronchial Hyperresponsiveness and Allergic Inflammation in a Mouse Model of Asthma

PURPOSE: Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma. METHODS: BALB/c mice were injected intraperitoneally with sMA followed by sensitization and challenge with ovalbumin (OVA). Mice were examined for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells into the lung tissues, histopathological changes in the lungs and CD4+CD25+Foxp3+ T cells in the spleen, and examined the response after the depleting regulatory T cells (Tregs) with an anti-CD25mAb. RESULTS: Treatment of mice with sMA suppressed the asthmatic response, including BHR, bronchoalveolar inflammation, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment abrogated the suppressive effects of sMA in this mouse model of asthma and totally depleted CD4+CD25+Foxp3+ T cells in the spleen. CONCLUSIONS: sMA attenuated allergic inflammation in a mouse model of asthma, which might be related with CD4+CD25+Foxp3+ T cell.

Bacillus Calmette-Guerin Suppresses Asthmatic Responses via CD4+CD25+ Regulatory T Cells and Dendritic Cells

PURPOSE: Bacillus Calmette-Guerin (BCG) is known to suppress the asthmatic responses in a murine model of asthma and to induce dendritic cells (DCs) maturation. Mature DCs play a crucial role in the differentiation of regulatory T cells (Tregs), which are known to regulate allergic inflammatory responses. To investigate whether BCG regulates Tregs in a DCs-mediated manner, we analyzed in a murine model of asthma. METHODS: BALB/c mice were injected intraperitoneally with BCG or intravenously with BCG-stimulated DCs and then sensitized and challenged with ovalbumin (OVA). Mice were analysed for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. To identify the mechanisms, IgE, IgG1 and IgG2a in the serum were analysed and the CD25+ Tregs in the mice were depleted with anti-CD25 monoclonal antibody (mAb). RESULTS: BCG and the transfer of BCG-stimulated DCs both suppressed all aspects of the asthmatic responses, namely, BHR, the production of total IgE and OVA-specific IgE and IgGs, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment reversed these effects. CONCLUSIONS: BCG can attenuate the allergic inflammation in a mouse model of asthma by a Tregs-related mechanism that is mediated by DCs.

Lentinus edodes Suppresses Allergen-Induced Airway Hyperresponsiveness and Inflammation by Downregulating Nuclear Factor-kappa B Activity in a Murine Model of Allergic Asthma / 체질인류학회지

Medicinal mushrooms have been shown to have profound health promoting benefits. Among them, Lentinus edodes is well-known to have anti-tumor, anti-inflammatory, and immunomodulatory effects. The aim of the present study is to evaluate whether Lentinus edodes ethanol extract (LE) inhibit airway inflammatory response in a murine asthma model induced by exposure to ovalbumin (OVA). The pretreatment of LE substantially attenuated airway hyperresponsiveness and eosinophilic inflammation in OVA-challenged mice. In addition, the increased levels of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in bronchoalveolar lavage fluids at 48 h after OVA inhalation was significantly reduced by the administration of LE. Furthermore, LE suppressed OVA-induced activation of nuclear factor-kappa B and p38 mitogen-activated protein kinase in lung tissues. Taken together, it is proposed that LE may serve as an effective therapeutic agent for allergic airway disease.

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway

The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of PGD2 and LTC4 in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase Cgamma1 (PLCgamma1)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase and p38), and the nuclear factor-kappaB (NF-kappaB) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.

Evaluación de la expresión del factor de transcripción Yin-Yang-1 y su asociación con TGF-β en un modelo murino de inflamación alérgica pulmonar con diferentes grados de severidad / Evaluation of the expression of the transcription factor Yin-Yang-1: association with TGF-β in a lung allergic inflammation in a mouse model with different severity grades

Introducción. El asma alérgica es una de las enfermedades más prevalecientes en la edad pediátrica. Los mecanismos implicados en este padecimiento no han sido esclarecidos totalmente. Se sabe que el factor de crecimiento transformante-beta (TGF-β) juega un papel muy importante en la fisiopatología de esta enfermedad y que la activación del factor de trascripción Yin-Yang-1 (YY1) induce un aumento en la expresión de esta citocina. El factor YY1 también regula la expresión de otras citocinas involucradas en el asma tales como la IL-4 y la IL-10. El objetivo de este trabajo fue evaluarla asociación entre YY1 y TGF-β en un modelo murino de inflamación alérgica pulmonar. Métodos. Se trabajó con un modelo murino de inflamación alérgica pulmonar con diferentes grados de severidad empleando ovalbúmina como alérgeno. Posteriormente se obtuvo el tejido pulmonar, que fue incluido en parafina, se construyó un microarreglo del tejido en un equipo semiautomático y, mediante inmunohistoquímica, se evaluó la expresión de YY1 y de TGF-β La densidad de la expresión se midió de manera cuantitativa por métodos computarizados. Resultados. Se observó inflamación alérgica pulmonar diferencial acorde con el grado de severidad del modelo; se observó el mismo patrón con la producción de moco. La expresión de ambas proteínas se correlacionó de manera directa con el grado de severidad de la inflamación alérgica pulmonar. Conclusiones. Los resultados obtenidos corroboran el papel que juegan ambas proteínas en la fisiopatología de la inflamación alérgica pulmonar.

Background. Allergic asthma is one of the most prevalent childhood diseases. This disease is characterized by airway inflammation and remodelling. The mechanisms implicated in the pathogenesis of this disease remain unclear. Several studies have shown that TGF-β plays an important role in the pathogenesis of asthma. In addition, the polymorphism of the TGF-β promoter region results in the overexpression of TGF-β via regulation of the transcription factor Yin-Yang-1 (YY1). It is has recently been demonstrated that YY1 may be involved in the pathogenesis of asthma by the regulation of IL-4 and IL-10. The aim of this study was to evaluate the association between the YY1 and TGF-β expression levels in a murine model of lung allergic inflammation. Methods. In this study we used a lung allergic inflammatory murine model with different severity degrees. Tissue microarray technology and immunohistochemistry were used to evaluate YY1 and TGF-p expression. The density expression was measured by quantitative methods using specific software. Results. Expression of both proteins correlated with the degrees of severity of lung allergic inflammation. A similar result was observed with mucus production. Conclusions. These results corroborate the role of YY1 and TGF-p in the pathogenesis of this disease.

Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma / 소아과

PURPOSE: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. METHODS: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, IgG1, and IgG2a levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. RESULTS: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific IgG1 levels and increased serum IgG2a level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. CONCLUSION: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.

Eotaxinas en asma bronquial y poliposis nasal / The role of eotaxins in bronchial asthma and nasal polyposis

Durante la última década se han descubierto tres péptidos con actividad quimotáctica específica para los eosinófilos y que son miembros de la familia de las quimocinas. Estas citocinas inducen a los eosinófilos a realizar diferentes funciones como quimotaxis, migración transendotelial e inducción de la liberación de radicales de oxígeno. Como los eosinófilos infiltran tanto las vías aéreas de pacientes asmáticos como los pólipos nasales, se ha postulado que las eotaxinas pueden ser responsables del reclutamiento de estas células. Los eosinófilos tienen la propiedad de inducir remodelamiento de la matriz extracelular y daño tisular a través de la liberación de proteasas tóxicas, mediadores inflamatorios, citocinas y radicales de oxígeno. Por lo cual, el desarrollo de estrategias terapéuticas que inhiban el reclutamiento de estas células constituye una esperanza en el tratamiento de las enfermedades alérgicas. Este artículo revisa la función de las eotaxinas en asma y poliposis nasal, además de discutir el posible uso de antagonistas de CCR3, receptor de las eotaxinas, como una nueva modalidad terapéutica de asma y poliposis nasal.

Over the last few years, three specific eosinophil activating peptides, eotaxin-1, -2 and -3, members of the chemokine family have been identified. These cytokines exert a number of functions on eosinophils including chemotaxis, transendothelial migration and induction of the release of reactive oxygen species. Eosinophils are considered to play an important role in allergic disease by causing tissue damage through the release of toxic proteases, lipid mediators, cytokines and oxygen free radicals. This article reviews the role of eotaxins in asthma and nasal polyps. Discussion focuses on therapeutic guidelines, particularly as it has been shown that CCR3, the major chemokine receptor in eosinophils, serves as a eotaxin receptor.

Sampledrawing from animal models of allergic airway inflammation / 医学研究生学报

Objective: Sampledrawing is an important procedure in the study of allergic airway inflammation.The authors investigate the methods of drawing samples from the animals with allergic airway inflammation.Methods: We included in this study 20 Guinea pigs,10 rats and 20 mice,which underwent trachea incision,followed by bronchoalveolar and rhinal lavage and collection of the lavage fluids.Then we collected blood samples via the heart from the guinea pigs and rats and via both the heart and the eyes from the mice,and obtained the tissues of the nasal cavities and lungs by different methods.Results: All the samples were satisfactorily obtained from the animals,and 80% of the bronchoalveolar and rhinal lavage fluids were collected.Conclusion: Different methods should be adopted to suit different sampledrawing from the animal models of allergic airway inflammation.