OBJECTIVE: To explore the effect of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice. METHODS: Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated. RESULTS: TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05). CONCLUSION Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.
Animals ; Asthma/chemically induced* ; Inflammation ; Macrophages ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases ; Respiratory System ; Toluene 2,4-Diisocyanate/adverse effects*

This study investigated the effect of Maxing Shigan Decoction(MXSGD) and its disassembled prescriptions against the airway inflammation in respiratory syncytial virus(RSV)-aggravated asthma and the regulation of transient receptor potential vanilloid-1(TRPV1). To be specific, ovalbumin(OVA) and RSV were used to induce aggravated asthma in mice(female, C57BL/6). Then the model mice were intervened by MXSGD and the disassembled prescriptions. The eosinophil(EOS) in peripheral blood, inflammatory cells in bronchoalveolar lavage fluid(BALF), enhanced pause(Penh) variation, and lung pathological damage in each group were observed, and the changes of interleukin(IL)-4, IL-13, substance P(SP), and prostaglandin E2(PGE2) in BALF were mea-sured by enzyme-linked immunosorbent assay(ELISA). Quantitative real time polymerase chain reaction(qPCR) and Western blot were used to detect mRNA and protein of TRPV1 in mouse lung tissue. In the in vitro experiment, 16 HBE cells were stimulated with IL-4 and RSV. Then the changes of TRPV1 expression after the intervention with the serum containing MXSGD and its disassembled prescriptions were observed. Besides, the intracellular Ca~(2+) level after the stimulation with TRPV1 agonist was evaluated. The results showed that the mice in the model group had obvious asthma phenotype, the levels of various inflammatory cells in the peripheral blood and BALF and Penh were significantly increased(P<0.05, P<0.01), and the lung tissue was severely damaged compared with the control group. Compared with the model group, the levels of EOS in the peripheral blood and BALF were significantly decreased in the MXSGD group, the SG group and the MXC group(P<0.05, P<0.01). The levels of WBC and neutrophils in BALF were significantly decreased in the MXSGD group and SG group(P<0.01), the levels of neutrophils in BALF were decreased in the MXC group(P<0.05). The improvement effect of the MXGSD on the level of inflammatory cells in peripheral blood and BALF was better than that of two disassembled groups(P<0.05, P<0.01). After 50 mg·mL~(-1) acetylcholine chloride stimulation, the Penh values of the MXSGD group and the MXC group significantly decreased(P<0.01), and the Penh value of the SG group decreased(P<0.05). The levels of IL-4, IL-13, PGE2 and SP in BALF could be significantly decreased in the MXSGD group(P<0.05, P<0.01), the levels of IL-13 and PGE2 in BALF could be decreased in the MXC group(P<0.05, P<0.01), and the levels of IL-13, PGE2 and SP in BALF could be decreased in the SG group(P<0.05, P<0.01). MXSGD could down-regulate the protein and mRNA expression of TRPV1 in lung tissue(P<0.05, P<0.01). The serum containing MXSGD and its disassembled prescriptions could down-regulate TRPV1 expression in 16 HBE cells stimulated by IL-4 combined with RSV and inhibit the inward flow of Ca~(2+) induced by TRPV1 agonist, especially the serum containing MXSGD which showed better effect than the serum containing disassembled ones(P<0.05). In vivo and in vitro experiments verified the protective effect of MXSGD and its disassembled prescriptions against airway inflammation in RSV-exacerbated asthma, the whole decoction thus possessed synergy in treating asthma, with better performance than the dissembled prescriptions. Different groups of prescription had made contributions in improving airway hyperresponsiveness, anti-allergy and anti-inflammation. The mechanism is the likelihood that it regulates TRPV1 channel and levels of related inflammatory mediators.
Female ; Mice ; Animals ; Interleukin-13/metabolism* ; Interleukin-4/metabolism* ; Dinoprostone ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Asthma/chemically induced* ; Lung ; Bronchoalveolar Lavage Fluid ; Ovalbumin/adverse effects* ; Inflammation/metabolism* ; RNA, Messenger/metabolism* ; Prescriptions ; Disease Models, Animal ; TRPV Cation Channels/metabolism*

OBJECTIVES: The association between concentrations of sulfur dioxide (SO), nitrogen dioxide (NO), carbon monoxide (CO), ozone (O), and emergency ambulance dispatches (EADs) for asthma was explored in the central Sichuan Basin of southwestern China for the first time. METHODS: EADs for asthma were collected from the Chengdu First-Aid Command Center. Pollutant concentrations were collected from 24 municipal environmental monitoring centers and including SO, NO, CO, daily 8-h mean concentrations of O (O-8 h), and particulate matter less than 2.5 μm in aerodynamic diameter (PM). The climatic data were collected from the Chengdu Municipal Meteorological Bureau. All data were collected from years spanning 2013-2017. A time-stratified case-crossover design was used to analyze the data. RESULTS: After controlling for temperature, relative humidity, and atmospheric pressure, IQR increases in SO (13 μg/m), NO (17 μg/m), and CO (498 μg/m) were associated with 18.8%, 11.5%, and 3.1% increases in EADs for asthma, respectively. The associations were strongest for EADs and SO, NO, and CO levels with 3-, 5-, and 1-day lags, respectively. CONCLUSIONS This study provides additional data to the limited body of literature for potential health risks arising from ambient gaseous pollutants. The results of the study suggest that increased concentrations of SO, NO, and CO were positively associated with emergency ambulance dispatches for asthma in Chengdu, China. Further studies are needed to investigate the effects of individual air pollutants on asthma.
Air Pollutants ; analysis ; toxicity ; Asthma ; chemically induced ; epidemiology ; Carbon Monoxide ; analysis ; toxicity ; China ; epidemiology ; Cities ; Cross-Over Studies ; Emergency Medical Dispatch ; statistics & numerical data ; Environmental Monitoring ; statistics & numerical data ; Humans ; Nitrogen Dioxide ; analysis ; toxicity ; Ozone ; analysis ; toxicity ; Particle Size ; Particulate Matter ; analysis ; toxicity ; Risk ; Sulfur Dioxide ; analysis ; toxicity

To explore the therapeutic effect of honokiol on particulate matter 2.5 (PM2.5)-induced lung injury in asthmatic mice and the possible mechanisms.
 Methods: A total of 32 BALB/C mice were randomly divided into four groups: a normal saline group, a model group, a PM2.5 group and a honokiol group (n=8 in each group). The asthma mouse model was established by ovalbumin treatment. The mice were treated with physiological saline, ovalbumin, PM2.5 and honokiol, respectively. Lung tissues and serum were collected. The pathological changes of lung tissues were evaluated. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were measured and the expressions of Toll like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), retinoid-related orphan receptor gamma-t (RORγt) and forkhead box protein 3 (Foxp3) in lung tissues were detected.
 Results: 1) The lung tissues of mice in the asthma group showed obvious pathological changes and inflammatory state, suggesting that the asthma model was established successfully. PM2.5 could aggravate the pathological condition of inflammatory injury in lung tissues in asthmatic mice. 2) Compared to the PM2.5 group, the pathological symptoms in the lung tissues were alleviated in the honokiol group and the percentage of inflammatory cells in BALF and the levels of inflammatory cytokines in BALF and serum were significantly reduced (all P<0.05). 3) Compared to the PM2.5 group, the expressions of TLR4, NF-κB (p-p65) and RORγt in lung tissues were significantly decreased, while the expression of Foxp3 was increased; the ratio of RORγt/Foxp3 was also decreased in the honokiol group (all P<0.05).
 Conclusion: Honokiol can resist lung injury induced by PM2.5 in asthmatic mice. These effects are through inhibiting TLR4-NF-κB pathway-mediated inflammatory response or regulating the balance of Th17/Treg cells.
Animals ; Asthma ; chemically induced ; complications ; Biphenyl Compounds ; pharmacology ; Bronchoalveolar Lavage Fluid ; chemistry ; Cytokines ; analysis ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Inflammation Mediators ; analysis ; Lignans ; pharmacology ; Lung ; metabolism ; pathology ; Lung Injury ; drug therapy ; etiology ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; NF-kappa B ; metabolism ; Ovalbumin ; Particulate Matter ; toxicity ; Random Allocation ; Toll-Like Receptor 4 ; metabolism

PURPOSE: The study aims to classify schools based on traffic pollutants and their complex sources, to assess the environment, to determine the state of allergic diseases among students using the International Study of Asthma and Allergies in children (ISAAC) questionnaire, and to assess their connection to air pollutants. MATERIALS AND METHODS: A total of seven schools were divided into three categories according to the characteristics of their surrounding environments: three schools in traffic-related zones, two schools in complex source zones I (urban), and two schools in complex source zones II (industrial complex). ISAAC questionnaires were administered and the 4404 completed questionnaires were analyzed. RESULTS: The frequency of asthma treatment during the past 12 months showed a significant increase (p<0.05) with exposure to NO2 [1.67, 95% confidence intervals (CIs) 1.03-2.71] in the complex source zones. The frequency of allergic rhinitis treatment during the past 12 months increased significantly with exposure to Black Carbon (1.60, 95% CIs 1.36-1.90) (p<0.001), SO2 (1.09, 95% CIs 1.01-1.17) (p<0.05), NO2 (1.18, 95% CIs 1.07-1.30) (p<0.01) for all subjects. CONCLUSION: In terms of supporting children's health, care, and prevention related to major spaces for children, such as school zones, spaces used in coming to and leaving school, playgrounds, and classrooms are essential to ensuring not only the safety of children from traffic accidents but also their protection from local traffic pollutants and various hazardous environmental factors.
Adolescent ; Air Pollutants/*adverse effects ; Air Pollution/*adverse effects ; Asthma/chemically induced/*epidemiology/*etiology ; Child ; Cross-Sectional Studies ; *Environmental Exposure ; Female ; Humans ; Male ; Republic of Korea/epidemiology ; Rhinitis, Allergic, Perennial/chemically induced/*epidemiology ; Schools ; Surveys and Questionnaires ; Vehicle Emissions/analysis/toxicity

BACKGROUND/AIMS: Asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Peroxisome proliferator-activated receptors have been reported to regulate inflammatory responses in many cells. In this study, we examined the effects of intranasal rosiglitazone on airway remodeling in a chronic asthma model. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated intranasally with rosiglitazone with or without an antagonist during OVA challenge. We determined airway inflammation and the degree of airway remodeling by smooth muscle actin area and collagen deposition. RESULTS: Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, compared with control mice. Additionally, the mice developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of rosiglitazone intranasally inhibited the eosinophilic inflammation significantly, and, importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. Expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) was increased in the OVA group and decreased in the rosiglitazone group. Co-treatment with GW9660 (a rosiglitazone antagonist) and rosiglitazone increased the expression of TLR-4 and NF-kappaB. CONCLUSIONS: These results suggest that intranasal administration of rosiglitazone can prevent not only air way inf lammation but also air way remodeling associated with chronic allergen challenge. This beneficial effect is mediated by inhibition of TLR-4 and NF-kappaB pathways.
Actins/metabolism ; Administration, Inhalation ; Airway Remodeling/*drug effects ; Animals ; Anti-Asthmatic Agents/*administration & dosage ; Asthma/chemically induced/*drug therapy/metabolism/physiopathology ; Chronic Disease ; Collagen/metabolism ; Disease Models, Animal ; Female ; Lung/*drug effects/metabolism/physiopathology ; Mice, Inbred BALB C ; NF-kappa B/metabolism ; Ovalbumin ; PPAR gamma/agonists/metabolism ; Pneumonia/chemically induced/physiopathology ; Pulmonary Eosinophilia/chemically induced/prevention & control ; Signal Transduction/drug effects ; Thiazolidinediones/*administration & dosage ; Toll-Like Receptor 4/metabolism

To determine the correlation between the working environment and the health status of employees in solar greenhouse, 1171 employees were surveyed. The results show the 'Greenhouse diseases' are affected by many factors. Among general uncomforts, the morbidity of the bone and joint damage is the highest and closely related to labor time and age. Planting summer squash and wax gourd more easily cause skin pruritus. Asthma-related cough, eye disease, and skin pruritus are significantly correlated with the cultivation of wax gourd. The application of inorganic fertilizer and fertigation dramatically induce the bone and joint damage. The smell of covering film greatly influence skin pruritus. Personal protection is badly scanty and normative occupational health and safety need to be completed.
Adult ; Asthma ; chemically induced ; Cough ; chemically induced ; Crops, Agricultural ; Educational Status ; Environment, Controlled ; Eye Diseases ; chemically induced ; Fertilizers ; toxicity ; Humans ; Middle Aged ; Nose Diseases ; chemically induced ; Occupational Exposure ; Pesticides ; toxicity ; Pruritus ; chemically induced ; Risk Factors ; Stomach Diseases ; chemically induced ; Workplace

Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1beta and interferon-gamma levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.
Animals ; Asthma/*chemically induced/pathology ; Female ; Inflammation/*chemically induced/pathology ; Interferon-gamma/analysis ; Interleukins/analysis ; Lung/drug effects/*pathology ; Mice, Inbred BALB C ; Nanoparticles/*adverse effects/chemistry ; Ovalbumin/adverse effects ; Polyethylene Glycols/adverse effects/chemistry ; Silicon Dioxide/*adverse effects/chemistry ; Surface Properties

OBJECTIVETo investigate the effect of chloroquine on airway hyperresponsiveness in asthmatic mice and explore the possible mechanism.

METHODSBalb/c mouse models of asthma established using OVA received intraperitoneal injections of chloroquine, dexamethasone, or both prior to OVA challenge. Within 24 h after the final challenge, airway hyper- responsiveness (AHR) of the mice was assessed, and the total cell count and the counts of different cell populations in the bronchoalveolar lavage fluid (BALF) were determined under light microscopy. The severity of lung inflammation was evaluated using HE staining, and the concentrations of IL-6 and PGF2α in the BALF were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSChloroquine pretreatment significantly decreased AHR (P<0.001) in the asthmatic mice and reduced the total cell count (P<0.01), eosinophils (P<0.001), neutrophils (P<0.01), and PGF2α levels in the BALF. Chloroquine combined with low-dose dexamethasone significantly lessened inflammations around the bronchioles (P<0.05) and blood vessels (P<0.01) in the lung tissue, and obviously lowered IL-6 (P<0.05) and PGF2α (P<0.001) in the BALF in the asthmatic mice.

CONCLUSIONChloroquine can inhibit AHR in asthmatic mice and produce better anti-inflammatory effect when combined with dexamethasone for treatment of neutrophilic asthma.

Animals ; Asthma ; chemically induced ; drug therapy ; Bronchoalveolar Lavage Fluid ; cytology ; Chloroquine ; pharmacology ; Dexamethasone ; pharmacology ; Dinoprost ; metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; cytology ; Inflammation ; pathology ; Interleukin-6 ; metabolism ; Leukocyte Count ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; Neutrophils ; cytology

The aim of the study was to investigate the anti-asthmatic effects of oxymatrine (OXY) and the possible underlying mechanisms. The mouse asthma model was established by ovalbumin (OVA) intraperitoneal injection. A total of fifty mice were randomly assigned to five groups: control, OVA, OVA + dexamethasone (Dex, 2 mg · kg(-1)), and OVA + OXY (40 mg · kg(-1)), and OVA + OXY (80 mg · kg(-1)), respectively. Histological studies were conducted by the hematoxylin and eosin (HE) staining, the levels of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13, and IgE were evaluated by enzyme-linked immunosorbent assay (ELISA), and the protein level of CD40 was analyzed by Western blotting. OXY inhibited OVA-induced increases in eosinophil count; the levels of IL-4, IL-5, IgE, and IL-13 were recovered. It also substantially inhibited OVA-induced eosinophilia in lung tissues and the expression of CD40 protein. These findings suggest that OXY may effectively ameliorate the progression of asthma and could be explored as a possible therapy for patients with allergic asthma.
Alkaloids ; pharmacology ; Animals ; Anti-Asthmatic Agents ; pharmacology ; Anti-Inflammatory Agents ; pharmacology ; Asthma ; drug therapy ; Bronchoalveolar Lavage Fluid ; chemistry ; CD40 Antigens ; metabolism ; Dexamethasone ; pharmacology ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Female ; Immunoglobulin E ; metabolism ; Interleukins ; metabolism ; Irritants ; toxicity ; Mice, Inbred BALB C ; Ovalbumin ; toxicity ; Pulmonary Eosinophilia ; chemically induced ; drug therapy ; Quinolizines ; pharmacology ; Random Allocation ; Signal Transduction ; drug effects