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

OBJECTIVEThe aim of the study was to investigate whether Orai1 antibody intraperitoneal injection could improve the condition of allergic rhinitis (AR) in mice.

METHODSTwenty-four BALB/C mice (SPF grade) were classified into 4 groups (AR group, Control group, Experimental group 1 and experimental group 2) according to a random number table. A mouse model of AR was established (Control group was established by phosphate buffered solution), and experimental group 1 and Experimental group 2 were established through intraperitoneal injection of 100 μg and 150 μg Orai1 antibody respectively. The number of sneezing and rubbing and eosinophilia in mice were assessed after different doses of Orai1 antibody intraperitoneal injection were applied. Then Orai1 protein and its mRNA in nasal mucosa, histomine, eosionphil cation protein (ECP), interlukin (IL)-1β, IL-4, IL-5 and IL-6 and their mRNA in nasal lavage fluid (NLF) and nasal mucosa were evaluated using enzyme linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). Furthermore, Orai1 protein and its mRNA in Th2 cells in peripheral blood, IL-4 and IL-5 in peripheral serum and their mRNAs in Th2 cells were also examined through ELISA and real-time RT-PCR. The data were analyzed by a statistical software of Graph Pad Prism 5.

RESULTSThere were significant differences in sneezing, nasal rubbing and local invading eosinophils in nasal mucosa after the treatment (t100 μg=7.88, t100 μg=9.92, t100 μg=4.30, respectively; t150 μg=16.43, t150 μg=16.31, t150 μg=9.35, respectively, all P-values<0.01). The Orai1 antibody intervention decreased contents of Orai1 in nasal mucosa, histomine, ECP, IL-1β, IL-4, IL-5 and IL-6. The contents of experimental group 1 were (0.186±0.015) μg/ml, (6.618±0.180) ng/ml, (2.555±0.031) ng/ml, (85.26±2.94) pg/ml, (55.12±1.21) pg/ml, (58.45±2.11) pg/ml and (77.12±2.13) pg/ml, respectively. The contents of experimental group 2 were (0.089±0.003) μg/ml, (4.501±0.310) ng/ml, (1.260±0.017) ng/ml, (48.49±2.12) pg/ml, (33.15±0.87) pg/ml, (38.24±0.95) pg/ml and (51.72±0.81) pg/ml, respectively. The differences were siginificant between group 1, group 2 and AR group(t value was 3.29, 10.44, 9.45, 17.53, 74.53, 87.06, 3.98; 8.54, 13.32, 23.00, 20.89, 80.73, 103.70, 13.34, all P<0.01). However, there were no significant differences in Orai1 protein and its mRNA in peripheral Th2 cells, IL-4 and IL-5 in peripheral serum and their mRNAs in Th2 cells (all P-values>0.05). In addition, the effect of 150 μg Orai1 antibody treatment was better than 100 μg one (all P-values<0.05).

CONCLUSIONOrai1 antibody intraperitoneal injection can improve the symptoms of AR mice, and alleviate the condition of allergic inflammation. Orai1 may become a novel aim in the AR study.

Animals ; Antibodies ; pharmacology ; Calcium Channels ; immunology ; metabolism ; Cytokines ; immunology ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Eosinophilia ; therapy ; Eosinophils ; immunology ; Immunotherapy ; Inflammation ; Injections, Intraperitoneal ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa ; metabolism ; ORAI1 Protein ; RNA, Messenger ; Rhinitis, Allergic ; therapy ; Th2 Cells ; immunology

BACKGROUND/AIMS: Pleuropulmonary paragonimiasis produces no specific symptoms or radiologic findings, allowing for the possibility of misdiagnosis. We evaluated the specific clinical and pleural fluid features of pleuropulmonary paragonimiasis masquerading as pleural tuberculosis. METHODS: We retrospectively analyzed the clinical and radiologic characteristics of 20 patients diagnosed with pleuropulmonary paragonimiasis between 2001 and 2011. RESULTS: In total, 17 patients presented with respiratory symptoms, including dyspnea (30%), hemoptysis (20%), cough (20%), and pleuritic chest pain (15%). Chest radiographs revealed intrapulmonary parenchymal lesions, including air-space consolidation (30%), nodular opacities (20%), cystic lesions (15%), ground-glass opacities (10%), and pneumothorax (5%). A pleural f luid examination revealed eosinophilia, low glucose levels, and high lactate dehydrogenase (LDH) levels in 87%, 76%, and 88% of the patients, respectively. These traits helped to distinguish pleuropulmonary paragonimiasis from other pleural diseases such as parapneumonic effusion, malignancy, and pleural tuberculosis. CONCLUSIONS: Pleuropulmonary paragonimiasis is often initially misdiagnosed as other pleural diseases. Therefore, it is important to establish the correct diagnosis. In patients with unexplained pleural effusion living in paragonimiasis-endemic areas, pleural fluid obtained by thoracentesis should be examined to distinguish pleuropulmonary paragonimiasis. When marked eosinophilia, high LDH levels, and low glucose levels are identified in pleural fluid, physicians could consider a diagnosis of pleuropulmonary paragonimiasis.
Adolescent ; Adult ; Aged ; Animals ; Biological Markers/analysis ; Child ; Child, Preschool ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Eosinophilia/diagnosis/parasitology ; Female ; Glucose/analysis ; Humans ; L-Lactate Dehydrogenase/analysis ; Lung Diseases, Parasitic/*diagnosis/metabolism/parasitology/radiography ; Male ; Middle Aged ; Paracentesis ; Paragonimiasis/*diagnosis/metabolism/parasitology/radiography ; Paragonimus westermani/*isolation & purification ; Pleural Effusion/*diagnosis/metabolism/parasitology/radiography ; Predictive Value of Tests ; Retrospective Studies ; Tomography, X-Ray Computed ; Tuberculosis, Pleural/*diagnosis ; Young Adult

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

This study was aimed to investigate the abnormal expression of PDGFRA gene in eosinophilia by FISH. Translocations of PDGFRA gene in 13 patients with eosinophilia were detected by using 4q12 three-color probe and FISH technology. Fifteen people were used as control to establish the normal cut-off value of fluorescence signal of PDGFRA. The results indicated that 1 out of 13 patients with eosinophilia was corrected and was diagnosed as CML. The fusion gene of FIP1L1-PDGFRA (F/P) was found in 2 patients and the positive rate of F/P fusion gene detected by probe 4q12 was 17% in the 12 patients with eosinophilia. Other translocation forms involving PDGFRA gene were not found. It is concluded that a variety of translocation forms of PDGFRA gene can be detected in patients with eosinophilia by using 4q12 three-color probe and FISH technology, which can provide important information for assessing diagnosis and treatment.
Chromosomes, Human, Pair 4 ; Eosinophilia ; metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Oncogene Proteins, Fusion ; Receptor, Platelet-Derived Growth Factor alpha ; genetics ; Translocation, Genetic

Polyvinyl chloride (PVC) is a widely used chemical for production of plastics. However occupational asthma (OA) caused by PVC has been reported only rarely. We report a 34-yr-old male wallpaper factory worker with OA due to PVC and nickel (Ni) whose job was mixing PVC with plasticizers. He visited the emergency room due to an asthma attack with moderate airflow obstruction and markedly increased sputum eosinophil numbers. A methacholine challenge test was positive (PC20 2.5 mg/mL). Bronchoprovocation tests with both PVC and Ni showed early and late asthmatic responses, respectively. Moreover, the fractional concentration of exhaled nitric oxide (FeNO) was increased after challenge with PVC. To our knowledge, this is the first case of OA in Korea induced by exposure to both PVC and Ni. We suggest that eosinophilic inflammation may be involved in the pathogenesis of PVC-induced OA and that FeNO monitoring can be used for its diagnosis.
Adult ; Asthma, Occupational/*chemically induced/*diagnosis ; Breath Tests ; Bronchial Provocation Tests ; Environmental Exposure ; Eosinophilia/*diagnosis ; Exhalation ; Humans ; Leukocyte Count ; Male ; Nickel ; Nitric Oxide/metabolism ; Occupational Exposure ; Plasticizers ; Polyvinyl Chloride

OBJECTIVETo study the clinicopathologic features, diagnosis and differential diagnosis of epithelioid hemangioma.

METHODSThe morphologic features of 7 cases of epithelioid hemangioma of skin, bone and venous vessels were studied.

RESULTSThere were altogether 4 male and 3 female patients (median age = 34 years; age range from 14 to 54 years). The 3 skin cases presented as single or multiple erythematous to bluish nodules or papules, with or without itchiness. The 2 bone cases appeared as osteolytic expansile lesions on radiologic examination. The remaining 2 cases involved medium-sized venous structures and presented as small isolated nodules in soft tissue. Histologically, the lesions were characterized by the presence of exuberant endothelial proliferations with various degree of inflammatory reaction. The neoplastic endothelial cells were plump, eosinophilic and polygonal, forming vascular channels. Occasional solid sheet-like arrangement was demonstrated. Intracytoplasmic vacuoles were commonly identified, indicating formation of primary lumen. The surrounding stroma contained various number of eosinophils and lymphoplasmacytic cells. Immunohistochemical study showed that the tumor cells were positive for endothelial markers (CD31 and CD34) and negative for epithelial marker (cytokeratin). Follow-up information was available in 6 cases. The duration of follow-up ranged from 5 to 36 months (median = 14 months). There was no evidence of recurrence or distant metastasis.

CONCLUSIONSEpithelioid hemangioma is a rare benign curable lesion which can be multifocal, involving skin, soft tissue and bone. It needs to be distinguished from Kimura's disease and epithelioid hemangioendothelioma.

Adolescent ; Adult ; Angiolymphoid Hyperplasia with Eosinophilia ; pathology ; Antigens, CD34 ; metabolism ; Bone Neoplasms ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Hemangioendothelioma, Epithelioid ; pathology ; Hemangioma ; metabolism ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Skin Neoplasms ; metabolism ; pathology ; surgery

Carcinoma, Mucoepidermoid ; complications ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Diagnosis, Differential ; Eosinophilia ; complications ; metabolism ; pathology ; Epithelial Cells ; pathology ; Female ; Hashimoto Disease ; metabolism ; pathology ; surgery ; Humans ; Keratin-19 ; metabolism ; Membrane Proteins ; metabolism ; Middle Aged ; Thyroid Gland ; metabolism ; pathology ; surgery ; Thyroid Nodule ; metabolism ; pathology ; surgery ; Transcription Factors ; beta Catenin ; metabolism

OBJECTIVE: In this study, we investigated the anti-inflammation effects of Xuebijing in OVA-induced murine allergic rhinitis model. Furthermore, we determined whether heme oxygenase (HO)-1 is required for the protective activity of Xuebijing. METHOD: Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. Levels of interleukin IL-4, IL-5, IL-13, and tumor necrosis factor (TNF)-alpha in nasal lavage fluid were measured using enzyme-linked immunosorbent assays (ELISAs). Lung tissue and nasal mucosa sections were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production, Immunohistochemistry, Real-time PCR and Western Blot analyses for HO-1 protein expression. RESULT: Orally administered Xuebijing significantly inhibited the number of OVA-induced inflammatory cells and IgE production, along with reduced T-helper (Th) 2 cytokine levels, such as IL-4, IL-5 and IL-13, improved the level of IFN-gamma, in nasal lavage fluid. In addition, Xuebijing induced a marked decrease in OVA-induced inflammatory cell infiltration and mucus production in nasal and lung tissues. These effects were correlated with HO-1 mRNA and protein induction. CONCLUSION Our results indicate that Xuebijing protects against OVA-induced airway inflammation, at least in part, via HO-1 upregulation.
Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Eosinophilia ; metabolism ; Heme Oxygenase-1 ; metabolism ; Immunoglobulin E ; immunology ; Inflammation ; drug therapy ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-5 ; metabolism ; Membrane Proteins ; metabolism ; Mice ; Nasal Mucosa ; metabolism ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; chemically induced ; drug therapy ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Recent clinical evidence indicates that the non-eosinophilic subtype of severe asthma is characterized by fixed airway obstruction, which may be related to emphysema. Transgenic studies have demonstrated that high levels of IFN-gamma in the airways induce emphysema. Fibroblast growth factor 2 (FGF2), which is the downstream mediator of TGF-beta, is important in wound healing. We investigated the role of FGF2 in IFN-gamma-induced emphysema and the therapeutic effects of recombinant FGF2 in the prevention of emphysema in a severe non-eosinophilic asthma model. To evaluate the role of FGF2 in IFN-gamma-induced emphysema, lung targeted IFN-gamma transgenic mice were cross-bred with FGF2-deficient mice. A severe non-eosinophilic asthma model was generated by airway application of LPS-containing allergens twice a week for 4 weeks. To evaluate protective effects of FGF2, recombinant FGF2 (10 microg) was injected subcutaneously during allergen challenge in the severe asthma model. We found that non-eosinophilic inflammation and emphysema induced by transgenic overexpression of IFN-gamma in the airways were aggravated by the absence of FGF2. Airway challenge with LPS-containing allergens induced more inflammation in mice sensitized with LPS-containing allergens compared to challenge with allergens alone. In addition, LPS-induced lung inflammation and emphysema depended on IFN-gamma but not on IL-13. Interestingly, emphysema in the severe asthma model was significantly inhibited by treatment with recombinant FGF2 during allergen challenge, whereas lung inflammation was unaffected. Therefore, our present data suggest that FGF2 may help protect against IFN-gamma-induced emphysema, and that recombinant FGF2 may help lessen the severity of emphysema.
Animals ; Asthma/drug therapy/*prevention & control ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Emphysema/drug therapy/*prevention & control ; Enzyme-Linked Immunosorbent Assay ; Fibroblast Growth Factor 2/deficiency/*metabolism/*therapeutic use ; Flow Cytometry ; Inflammation/immunology ; Interferon-gamma/*biosynthesis/genetics ; Interleukin-13 ; Lipopolysaccharides/administration & dosage/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pulmonary Eosinophilia ; Recombinant Proteins/administration & dosage/therapeutic use