Is there a correlation between the changes in airway inflammation and the changes in respiratory mechanics after vaping in patients with asthma?

BACKGROUND Electronic cigarettes(ECs)have been promoted as alternatives to traditional cigarettes.To investigate ECs’effects on respiratory system,especially in patients with respiratory diseases.METHODS We randomly selected 25 smokers with stable moderate asthma and matched them with 25 healthy smokers.All were subjucted to pulmonary function tests(PFTs),impulse oscillometry(IOS),fraction exhaled Nitric Oxide(FeNO),exhaled breathe condensate(EBC)and biomarker measurements before and after vaping one nicotinecontaining EC.RESULTS The increase in FeNO 30 minutes after EC,reflecting airway inflammation,significantly correlated with increase of residual volume(RV),total lung capacity,respiratory impedance at 5 Hz(Z5Hz)and respiratory resistance at 5 and 20 Hz(R5Hz and R20Hz).No significant correlations were found between EBC biomarkers'changes and respiratory mechanics.CONCLUSION This is the first study demonstrating that the changes in airway inflammation caused by EC have direct effects in respiratory mechanics of asthmatic patients.

Influence of Danshen Injection on airway inflammation and CD4^+ CD25^+ regulatory T cells of asthmatic rats

Objective： To investigate the influence of Danshen Injection on airway inflammation and CD4^＋CD25^＋ regulatory T cells（CD4^＋CD25^＋ Tr） of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods： 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids （BALF） were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain （HE）. Flow cytometry was used to detect the CD4^＋CD25^＋ Tr ratio in peripheral blood mononuclear cells （PBMCs）. Results： Total cell, the percentage of lymphocytes, neutrophils and eosinophils （Eos） in BALF of Danshen Injection-treated group were lower than that in asthma group （P〈0.05, P〈0.01）. Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4^＋CD25^＋ Tr of asthma group was lower than that of control and Danshen Injection treated group （P〈0.05）. Conclusion： Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4^＋CD25^＋ Tr.

Maternal Disononyl Phthalate Exposure Activates Allergic Airway Inflammation via Stimulating the Phosphoinositide 3-kinase/Akt Pathway in Rat Pups

Objective To evaluate the effect of diisononyl phthalate（DINP） exposure during gestation and lactation on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. Methods Female Wistar rats were treated with DINP at different dosages（0, 5, 50, and 500 mg/kg of body weight per day）. The pups were sensitized and challenged by ovalbumin（OVA）. The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin（HE） staining; and the relative cytokines in phosphoinositide 3-kinase（PI3K）/Akt pathway were measured by enzyme-linked immunosorbent assay（ELISA） and western blot analysis. Results There was no significant difference in DINP＇s effect on airway hyperresponsiveness（AHR） between male pups and female pups. In the 50 mg/（kg·d） DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance（RI） compared with those from controls（P〈0.05）. Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/（kg·d） DINP-treated group. However, in the 5 and 500 mg/（kg·d） DINP-treated pups, no significant effects were observed. Conclusion There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.

Effect of All-trans Retinoic Acid on Airway Inflammation in Asthmatic Rats and Its Mechanism

Summary: The inhibitive effects of all-trans retinoic acid (ARTA) on airway inflammation in asthmatic rats and its mechanism on the basis of the regulation of nuclear factor kappaB (NF-κB) were explored. Thirty-two SD rats were randomly divided into 4 groups: control group, asthma group, dexamethasone treatment group and retinotic acid treatment group. The total and differential cell counts in the collected bronchoalveolar lavage fluid (BALF) were measured. The pathological changes in lung tissues were estimated by scoring. The expression of NF-κB inhibitor (IκBa), NF-κB, intercellular adhering molecule-1 (ICAM-1) in lung tissue was detected by immunohistochemical method. The results showed that in the two treatment groups, the total cell counts and proportion of inflammatory cells in BALF were significantly reduced, but there was no significant difference in differential cell counts in BALF between them. The pathological changes in lung tissues in the treatment groups were significantly attenuated as compared with asthma group. Except the epithelial injury in retinotic acid treatment group was milder than in dexamethasone treatment group, the remaining lesions showed no significant difference between them. In the two treatment groups, the expression of IκBa was increased, while the expression of NF-κB and ICAM-1 decreased with the difference between the two groups being not significant. It was concluded that the similar anti-inflammatory effects and mechanism of ATRA on airway in asthmatic rats to those of dexamethasone were contributed to the increase of cytoplasmic IκBa content and suppression of NF-κB activation and expression.

Effects of Medication Use on Small Airway Function and Airway Inflammation in Patients with Clinically Controlled Asthma

Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of the forced expiratory curve(FEF25%–75%),percentage of eosinophil,concentrations of eosinophil cationic protein(ECP)and interleukin(IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone.Subsequently,acute exacerbations were compared between two groups during the 24-week follow-up period.Results FEF25%–75%in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone.Meanwhile,the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone.Additionally,the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.Conclusion Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations,presumably secondary to reduction in airway inflammation.

The influence of vitamin D3 on airway inflammation and osteopontin expression in cough variant asthma rats

Objective:To observe the effect of vitaminD3 on airway inflammation and osteopontin(OPN)expression on cough variant asthma(CVA)models.Methods:SD rats were randomly divided into blank group,model group and treatment group,each group with 10 rats.The CVA model was induced by intraperitoneal injection combined with aerosolized ovalbumin(OVA),the treatment group was given 100 mg/ml of vitaminD330 minutes before challenge by administered orally.Airway hyperreaction were measured by airway resistance after inhalation of acetylcholine(Ach).Wright-Gimsa staining was used to observe the inflammatory cells in bronchoalveolar lavage fluid(BALF).HE and PAS were used to observe the morphological changes of lung tissue.OPN expression was detected by immunohistochemistry.Results:1)Airway hyperreaction:airway resistance after inhalation Ach in model group and treatment group were significantly higher than that in blank group(P<0.01),airway resistance in treatment group were lower than that in model group(P<0.01);2)Classification of inflammatory cells:The percentage of macrophages,lymphocytes,neutrophils,and eosinophils in the BALF of the model group and the treatment group were increased compared with the blank group(P<0.01),furthermore,the number of treatment group were lower than the model group(P<0.05);3)Morphological changes of lung tissue:a large amount of inflammatory cells and goblet cell proliferation were observed in the lung tissue of the model group,and these changes were slight in treatment group compared with model group;OPN expression in lung tissue:The expression of OPN in model and treatment group were increased compared with blank group(P<0.05),and the treatment group was lower than that of model group(P<0.05).The OPN content was positively correlated with the percentage of inflammatory cells in BALF(P<0.05).Conclusions:Vitamin D3 can reduce airway hyperreaction and airway inflammation in CVA rats.The mechanism may be related to the intervention of OPN expression in lung tissue.

Effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor of chronic obstructive pulmonary disease rat

Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided into 5 groups:blank control group,COPD model group,Fufei Gushen Yin high,medium and low dose groups,10 rats in each group,except the blank control group,the remaining 4 groups were Smoked combined with lipopolysaccharide(LPS),cold air stimulation to create CODP rat model.After successful modeling,the blank control group and COPD model group were fed with distilled water 3ml/only,Fufei Gushen Yin high,medium and low dose groups were given 1.02,0.51,0.26g Chinese medicine granules/100g/day,respectively.2 times a day for 28 consecutive days.Samples were collected,hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect the tumor necrosis factor alpha(TNF-α)in the serum and right alveolar lavage fluid(BALF)of rats in each group.),the content of transforming growth factorβ1(TGF-β1),interleukin-17(IL-17A)and matrix metalloproteinase(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in the left lung tissue The expression level of real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)rat left lung tissue GRmRNA,immunohistochemistry(IHC)to determine the expression level of left lung tissue glucocorticoid receptor(GR).Results:The content of TNF-α,TGF-β1 and IL-17A in the serum of COPD rats in Fufei Gushen Yin high,medium and low dose groups and BALF were significantly reduced compared with the COPD model group(P<0.05);The expressions of TIMP-1 and MMP-9 in tissues were lower than those in COPD model group(P<0.05);the expressions of GRmRNA and GR in lung tissues were higher than those in COPD model group(P<0.05),and were higher in Fufei Gushen Yin Among the middle-and low-dose groups,the middle-dose group has the most significant effect.Conclusion:Fufei Gushen Decoction can inhibit the release of inflammatory factors in lung tissue of COPD rats,improve airway inflammation and remodeling,and increase hormone sensitivity.

Establishment of Allergic Airway Inflammation Model in Late-phase Response of Sprague-Dawley Rats

Objective To establish allergic airway inflammation model in late-phase airway reaction of Sprague-Dawley (SD) rats. Methods Thirty-six SD rats were randomly divided into three groups-, control group (Group Ⅰ) ,single challenge group (Group Ⅱ ),consecutive challenge group (Group Ⅲ). The rats in Group Ⅱ and Group Ⅲ were sensitized twice by injection of ovalbumin (OA) together with aluminum hydroxide and Bordetella pertussis as adjuvants, followed by challenge with aerosolized OA for 20 min once in Group Ⅱ or one time on each day for one week in, Group Ⅲ. The rats in Group Ⅰ received 0. 9% saline by injection and inhalation. Results Compared with group Ⅰ , there were positive symptoms observed in the group Ⅱ and group Ⅲ; the amount of total leucocytes and eosinophil percentage in brochoalveolar lavage fluid (BALF) significantly increased (P<0.05 or P<0. 01 respectively) in Group Ⅱ or Ⅲ ; histopathologic changes of lung showed acute allergic inflammation changes in Group Ⅱ: Disrupted epithelium damaged subepithelial structure and eosinophil infiltration in the airway wall. As for the Group Ⅲ, there were allergen- induced characteristic features of chronic allergic airways inflammation: hypertrophy and hyperplasia of bronchial smooth muscle, goblet cell hyperplasia, basement membrane thickening, eosinophil in filtration, edema. Conclusion The model of allergic airway inflammation in late-phase response of SD rats was successfully established by OA sensitization (twice) and consecutive challenge.

Experimental study on the regulation effect of Qiaoqin Qingfei agent on cough variant asthma based on airway neurogenic inflammation

Objective:To investigate the mechanism of regulation of airway neurogenic inflammation by Qiaoqin Qingfei agent in rats with cough variant asthma(CVA).Methods:48 SD rats were randomly divided into blank group,model group,montelukast sodium group(1.05 mg/kg)and high,medium and low dose groups(26,13,6.5 g/kg),with 8 rats in each group.The rat CVA model was established by the method of ovalbumin(OVA)combined with aluminum hydroxide(Al(OH)3)sensitization and repeated stimulation.From the second day of sensitization,the rat CVA model was given by gavage for 28 days.The pathological changes of lung tissue were observed under microscope by HE staining.The content changes of nerve growth factor(NGF)and substance P(SP)in alveolar lavage fluid(BALF)were determined by double-antibody sandwich ABC-ELISA,and the protein expression levels of NGF and SP in lung tissue were detected by immunohistochemistry.Results:Pathological findings showed significant inflammatory manifestations in the model group,and the inflammatory infiltration in the high-dose,medium-dose and low-dose groups of Qiaoqin Qingfei agent and montelukast sodium groups were alleviated to varying degrees.Compared with blank group,the protein expression levels of NGF and SP in lung tissue of model group were significantly increased(P<0.01).Compared with model group,the protein expression levels of NGF and SP in lung tissue and the contents of NGF and SP in alveolar lavage fluid in high-dose,medium-dose and low-dose groups and montelukast sodium group were significantly decreased(P<0.05).Conclusion:Qiaoqin Qingfei agent may reduce airway inflammation and relieve cough variant asthma by regulating the protein expression levels of NGF and SP in airway neurogenic inflammation.

Inhibition of NF-κB Expression and Allergen-induced Airway Inflammation in a Mouse Allergic Asthma Model by Andrographolide

Andrographolide from traditional Chinese herbal medicines previously showed it possesses a strong anti- inflammatory activity. In present study, we investigated whether Andrographolide could inhibit allergen-induced airway inflammation and airways hyper-responsiveness and explored the mechanism of Andrographolide on allergen-induced airway inflammation and airways hyper-responsiveness. After sensitized and challenged by ovalbumin, the BALB/c mice were administered intraperitoneally with Andrographolide. Hyper-responsiveness was recorded. The lung tissues were assessed by histological examinations. NF-κB in lung was determined by immunofluorescence staining and Western blotting. Treatment of mice with Androqrapholide displayed lower Penh in response to asthma group mice. After treatment with Andrographolide, the extent of inflammation and cellular infiltration in the airway were reduced. Andrographolide interrupted NF-κB to express in cell nucleus. The level of NF-κB expression was inhibited by Andrographolide. The data indicate that Andrographolide from traditional Chinese herbal medicines could inhibit extensive infiltration of inflammatory cells in lung and decrease airway hyperreactivity. Andrographolide could inhibit NF-κB expression in lung and suppress NF-κB expressed in the nucleus of airway epithelial cells.

CD69 expression on airway eosinophils and airway inflammation in a murine model of asthma

Background Asthma is a chronic airway disease with inflammation characterized by physiological changes （airway hyper-responsiveness, AHR） and pathological changes （inflammatory cells infiltration and mucus production）. Eosinophils play a key role in the allergic inflammation. But the causative relationship between eosinophils and airway inflammation is hard to prove. One of the reasons is lack of activation marker of murine eosinophils. We investigated the expression of CD69 on murine eosinophils in vitro, the relationship between the expression of CD69 on eosinophils from peripheral blood and bronchoalveolar lavage fluid and on airway inflammation in asthmatic mice. Methods Eosinophils from peripheral blood of IL-5 transgenic mice （NJ.1638） were purified. Mice were divided into five groups： wild type mice sensitized and challenged with saline （WS group）, wild type mice sensitized and challenged with ovalbumin （WO group）, IL-5^-/- mice sensitized and challenged with saline and transferred with purified eosinophils （ISE group）, IL-5^-/- mice sensitized and challenged with OVA and transferred with purified eosinophils （IOE group）, IL-5^-/- mice sensitized and challenged with OVA and transferred with purified eosinophils, pretreated with anti CD4 monoclonal antibody （IOE＋antiCD4mAb group）. IL-5^-/- mice were sensitized with OVA at day 0 and day 14, then challenged with OVA aerosol. On days 24, 25, 26 and 27 purified eosinophils were transferred intratracheally to IL-5^-/- mice. On day 28, blood and BALF were collected and CD69 expression on eosinophils measured by flowcytometry. Results Purified eosinophils did not express CD69. But eosinophils cultured with PMA＋MA, IFN- T, IL-5 or GM-CSF expressed CD69 strongly. Eosinophils from blood of WO, WS group did not express CD69 at all. The numbers of eosinophils in BALF of WO group, IOE group, ISE group and IOE＋antiCD4mAb group were significantly higher than in mice of WS group which did not have eosinophils at all. CD69 expression on eosinophils in BALF of IOE and WO groups was strong. Eosinophils in BALF of ISE and IOE＋antiCDmAb groups did not express CD69. The mucus production result was similar to CD69 expression. There were eosinophils infiltration in lung slides of all groups except WS group. Conclusion Activation in airway of eosinophils could directly lead to airway inflammation.

Protective Effect of Emodin against Airway Inflammation in the Ovalbumin-Induced Mouse Model

Objective： To investigate whether emodin exerts protective effects on mouse with allergic asthma. Methods： A mouse model of allergic airway inflammation was employed. The C57BL/6 mice sensitized and challenged with ovalbumin （OVA） were intraperitoneally administered 10 or 20 mg/kg emodin for 3 days during OVA challenge. Animals were sacrificed 48 h after the last challenge. Inflammatory cell count in the bronchoalveolar lavage fluid （BALF） was measured. The levels of interleukin （IL）-4, IL-5, IL-13 and eotaxin in BALF and level of immunoglobulin E （IgE） in serum were measured with enzyme-linked immuno sorbent assay kits. The mRNA expressions of IL-4, IL-5, home oxygenase （HO）-I and matrix metalloproteinase-9 （MMP- 9） were determined by real-time quantitative polymerase chain reaction. Results： Emodin induced significant suppression of the number of OVA-induced total inflammatory cells in BALF. Treatment with emodin led to significant decreases in the levels of IL-4, IL-5, IL-13 and eotaxin in BALF and total IgE level in serum. Histological examination of lung tissue revealed marked attenuation of allergen-induced lung eosinophilic inflammation. Additionally, emodin suppressed IL-4, IL-5 and MMP-9 mRNA expressions and induced HO-1 mRNA expression. Conclusion： Emodin exhibits anti-inflammatory activity in the airway inflammation mouse model, supporting its therapeutic potential for the treatment of allergic bronchial asthma.

Therapeutic Effects of DNA Vaccine on Allergen-Induced Allergic Airway Inflammation in Mouse Model

Vaccination with DNA encoding Dermatophagoides pteronyssinus group 2 （Der p 2） allergen previously showed its effects of immunologic protection on Der p 2 allergen-induced allergic airway inflammation in mice. In present study, we investigated whether DNA vaccine encoding Der p 2 could exert therapeutic role on allergen-induced allergic airway inflammation in mouse model and explored the mechanism of DNA vaccination in asthma specific-allergen immunotherapy. After sensitized and challenged by Der p 2, the BALB/c mice were immunized with DNA vaccine. The degrees of cellular infiltration were scored. IgE levels in serum and IL-4/IL-13 levels in BALF were determined by ELISA. The lung tissues were assessed by histological examinations. Expressions of STAT6 and NF-kB in lung were determined by immunohistochemistry staining. Vaccination of mice with DNA vaccine inhibited the development of airway inflammation and the production of mucin induced by allergen, and reduced the level of Der p 2-specific IgE level. Significant reductions of eosinophil infiltration and levels of IL-4 and IL-13 in BALF were observed after vaccination. Further more, DNA vaccination inhibited STAT6 and NF-kB expression in lung tissue in Der p 2-immunized mice. These results indicated that DNA vaccine encoding Der p 2 allergen could be used for therapy of allergen-induced allergic airway inflammation in our mouse model. Cellular ＆ Molecular Immunology.

DNA vaccine encoding Der p2 allergen down-regulates STAT6 expression in mouse model of allergen-induced allergic airway inflammation

Background Activation of signal transducer and activator of transcription 6 （STAT6） plays a critical role in the late phase of Th2-dependent allergy induction. STAT6 is essential to Th2 cell differentiation, recruitment, and effector function. Our previous study confirmed that DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. In the present study, we determined whether DNA vaccine encoding Dermatophagoides pteronyssinus group 2 （Der p2 ） could down-regulate the expression and activation of STAT6 in lung tissue from asthmatic mice. Methods After DNA vaccine immunization, BALB/c mice were sensitized by intmperitoneal injection and challenged by intranasal instillation of rDer p2. The levels of the cytokines IL-4 and IL-13 in BAL fluid were measured by enzyme-linked immunosorbent assay. The lung tissue was assessed by immunohistochemical staining with anti-STAT6. The protein expression of STAT6 was determined by Western blot. The activation of STAT6 binding ability was analyzed with electrophoretic mobility shift assay. Results DNA vaccine encoding Der p2 allergen effectively decreased the levels of IL-4 and IL-13 in the asthmatic mice. Histological evidence and Western blot showed that the expression of STAT6 in the DNA treated mice was markedly attenuated. STAT6 binding to specific DNA motif in lung tissue from the gene vaccinated mice was inhibited. Condusion DNA vaccine encoding Der p2 prevents allergic pulmonary inflammation probably by inhibiting the STAT6 signaling pathway in mice with Der p2 allergen-induced allergic airway infammafion.

Effects of Ligustrazine on Airway Inflammation in A Mouse Model of Neutrophilic Asthma

Objective: To investigate the effects of ligustrazine(LTZ) on airway inflammation in a mouse model of neutrophilic asthma(NA). Methods: Forty healthy C57 BL/6 female mice were randomly divided into 4 groups using a random number table, including the normal control, NA, LTZ and dexamethasone(DXM) groups, with 10 rats in each group. The NA mice model was established by the method of ovalbumin combined with lipopolysaccharide sensitization. At 0.5 h before each challenge, LTZ and DXM groups were intraperitoneally injected with LTZ(80 mg/kg) or DXM(0.5 mg/kg) for 14 d, respectively, while the other two groups were given the equal volume of normal saline. After last challenge for 24 h, the aerosol inhalation of methacholine was performed and the airway reactivity was measured. The bronchoalveolar lavage fluid(BALF) was collected. The Wright-Giemsa staining was used for total white blood cells and differential counts. The levels of cytokines interleukin(IL)-17 and IL-10 were detected by enzyme-linked immunosorbent assay. The pathological change of lung tissue was observed by hematoxylin eosin staining. Results: The airway responsiveness of the NA group was significantly higher than the normal control group(P<0.05), while those in the LTZ and DXM groups were significantly lower than the NA group(P<0.05). The neutrophil and eosinophil counts in the LTZ and DXM groups were significantly lower than the NA group(P<0.05), and those in the LTZ group were significantly lower than the DXM group(P<0.05). There were a large number of peribronchiolar and perivascular inflammatory cells in filtration in the NA group. The airway inflammation in the LTZ and DXM groups were significantly alleviated than the NA group. The infiltration in the LTZ group was significantly reduced than the DXM group. Compared with the normal control group, the IL-17 level in BALF was significantly increased and the IL-10 level in BALF was significantly decreased in the NA group(P<0.05). LTZ and DXM treatment significantly decreased IL-17 levels and increased IL-10 levels compared with the NA group(P<0.05), and the changes in the above indices were more significant in the LTZ group(P<0.05). Conclusion: LTZ could alleviate the airway inflammation in the NA mice model through increasing the IL-10 level and decreasing the IL-17 level.

Monocyte chemotactic protein-inducing protein 1 negatively regulating asthmatic airway inflammation and mucus hypersecretion involvingγ-aminobutyric acid type A receptor signaling pathway in vivo and in vitro

Background:Mounting evidence,consistent with our previous study,showed thatγ-aminobutyric acid type A receptor(GABAAR)played an indispensable role in airway inflammation and mucus hypersecretion in asthma.Monocyte chemotactic protein-inducing protein 1(MCPIP1)was a key negative regulator of inflammation.Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases.However,the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied.This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells,and its potential mechanism.Methods:In vivo,mice were sensitized and challenged by ovalbumin(OVA)to induce asthma.Airway inflammation and mucus secretion were analyzed.In vitro,BEAS-2B cells were chosen.Interleukin(IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells.MCPIP1 Lentiviral vector(LA-MCPIP1)and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells,respectively.MCP-1,thymic stromal lymphopoietin(TSLP),mucin 5AC(MUC5AC),MCPIP1,and GABAARβ2 expressions were measured in both lung and BEAS-2B cells.Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.Results:MCPIP1 was up-regulated by LA-MCPIP1(P<0.001)and plasmid-MCPIP1(P<0.001)in lung and cells,respectively.OVA-induced airway inflammation and mucus hypersecretion,OVA-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice(all P<0.001).IL-13-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells(all P<0.001).Conclusion:The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells,involving GABAAR signaling pathway.

Plasmacytoid dendritic cell deficiency in neonates enhances allergic airway inflammation via reduced production of IFN-α

Allergic asthma,a chronic inflammatory airway disease associated with type 2 cytokines,often originates in early life.Immune responses at an early age exhibit a Th2 cell bias,but the precise mechanisms remain elusive.Plasmacytoid dendritic cells(pDCs),which play a regulatory role in allergic asthma,were shown to be deficient in neonatal mice.We report here that this pDC deficiency renders neonatal mice more susceptible to severe allergic airway inflammation than adult mice in an OVA-induced experimental asthma model.Adoptive transfer of pDCs or administration of IFN-αto neonatal mice prevented the development of allergic inflammation in wild type but not in IFNAR1−/−mice.Similarly,adult mice developed more severe allergic inflammation when pDCs were depleted.The protective effects of pDCs were mediated by the pDC-/IFN-α-mediated negative regulation of the secretion of epithelial cell-derived CCL20,GM-CSF,and IL-33,which in turn impaired the recruitment of cDC2 and ILC2 cells to the airway.In asthmatic patients,the percentage of pDCs and the level of IFN-αwere lower in children than in adults.These results indicate that impairment of pDC-epithelial cell crosstalk in neonates is a susceptibility factor for the development of allergeninduced allergic airway inflammation.

Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating the SIRT2-p65 pathway

Exposure to particulate matter 2.5(PM2.5)potentially triggers airway inflammation by activating nuclear factor-κB(NF-κB).Sirtuin 2(SIRT2)is a key modulator in inflammation.However,the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied.Therefore,this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues.Subsequently,SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway.The activation of p65 triggered airway inflammation,increment of mucus secretion by goblet cells,and acceleration of tracheal stenosis.Meanwhile,p65 phosphorylation and acetylation,airway inflammation,and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5.Triptolide(a specific p65 inhibitor)reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure.Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.

The membrane-associated ubiquitin ligases MARCH2 and MARCH3 target IL-5 receptor alpha to negatively regulate eosinophilic airway inflammation

Interleukin 5(IL-5)plays crucial roles in type 2-high asthma by mediating eosinophil maturation,activation,chemotaxis and survival.Inhibition of IL-5 signaling is considered a strategy for asthma treatment.Here,we identified MARCH2 and MARCH3 as critical negative regulators of IL-5-triggered signaling.MARCH2 and MARCH3 associate with the IL-5 receptorαchain(IL-5Rα)and mediate its K27-linked polyubiquitination at K379 and K383,respectively,and its subsequent lysosomal degradation.Deficiency of MARCH2 or MARCH3 modestly increases the level of IL-5Rαand enhances IL-5-induced signaling,whereas double knockout of MARCH2/3 has a more dramatic effect.March2/3 double knockout markedly increases the proportions of eosinophils in the bone marrow and peripheral blood in mice.Double knockout of March2/3 aggravates ovalbumin(OVA)-induced eosinophilia and causes increased inflammatory cell infiltration,peribronchial mucus secretion and production of Th2 cytokines.Neutralization of Il-5 attenuates OVA-induced airway inflammation and the enhanced effects of March2/3 double deficiency.These findings suggest that MARCH2 and MARCH3 play redundant roles in targeting IL-5Rαfor degradation and negatively regulating allergic airway inflammation.

Comparison of effect of granules and herbs of Bu-Shen-Yi-Qi-Tang on airway inflammation in asthmatic mice

Background Bu-Shen-Yi-Qi-Tang （BSYQT）,which is prescribed on the basis of clinical experience,is commonly used in clinics of traditional Chinese medicine （TCM） for asthma treatment.The components of BSYQT include Radix Astragali （RA）,Herba Epimedii （HE） and Radix Rehmanniae （RR）.The aim of this study was to compare the effect of granules and herbs of BSYQT on airway inflammation in asthmatic mice.Methods Sixty female BALB/c mice were randomly divided into the normal control （NC） group,asthmatic group （A）,decoction of granules of BSYQT treatment group （GD）,decoction of herbs of BSYQT treatment group （HD）,and dexamethasone treatment group （DEX）.The mouse asthmatic model was induced by ovalbumin （OVA） sensitization and challenge.GD and HD of BSYQT as well as DEX were prepared and administered by intragastric infusion.Airway hyperresponsiveness （AHR） to methacholine （Mch）,lung histopathology analysis,inflammatory mediators in serum （IL-4,IL-5,IL-17A,IFN-γ,and eotaxin） and in lung （IL-4,IL-5,IFN-γ,and eotaxin） were selected for investigation and comparison.Results Both GD and HD treatment could decrease airway resistance （RL） and increase dynamic compliance （Cdyn） to Mch compared with the A group （P ＜0.05）.HD treatment was more effective in RL reduction than Mch at doses of 3.125 and 6.25 mg/ml （P ＜0.05） and in Cdyn increase at Mch doses of 6.25 and 12.5 mg/ml （P ＜0.05）.There were no marked differences in RL reduction and Cdyn improvement between mice in HD and DEX groups （P ＞0.05）.Both GD and HD treatment markedly attenuated lung inflammation （P ＜0.05）,and HD treatment demonstrated more significant therapeutic function in alleviating lung inflammation than that of GD and DEX treatment （P ＜0.05）.Both GD and HD treatment resulted in a significant reduction in IL-4 and IL-17A levels and an increase in the IFN-γ level in serum compared with the A group （P ＜0.05）.The effect of HD in lowering the IL-4 and IL-17A level was significantly greater than that of GD （P ＜0.05）,and was not significantly different from DEX （P ＞0.05）.HD treatment significantly reduced the serum level of IL-5 and eotaxin compared with the A group （P ＜0.05）,however,mice in the GD treatment group did not demonstrate this effect.GD and HD treatment significantly reduced IL-4 and eotaxin mRNA expression compared with the A group （P ＜0.05）.HD treatment significantly reduced IL-5 mRNA expression compared with the A group （P ＜0.05）.There was a significant difference between the GD and HD treatment groups in reducing IL-5 and eotaxin mRNA expression （P ＜0.05）.HD treatment was more effective in down-regulation of IL-5 in serum and eotaxin level both in serum and lung than DEX （P ＜0.05）.Compared with the A group,an obvious increase in mRNA expression of IFN-γ was observed in both the GD and HD treatment groups （P ＜0.05）.However,the effect of HD treatment on increase of IFN-γ mRNA expression was more apparent than GD and DEX treatment （P ＜0.05）.Conclusions Both GD and HD treatment could decrease AHR,attenuate lung inflammation,reduce IL-4,IL-5,IL-17A,and eotaxin levels and increase IFN-γ levels in asthmatic mice.HD treatment manifests more remarkable inhibitory effects on asthmatic inflammation than GD treatment,which could provide a guide for further research on the screening of the material basis of the best anti-inflammatory effect of BSYQT.