ABSTRACT
STUDY OBJECTIVE: Several lung diseases are characterized by the presence of increased numbers of activated macrophages. The recruitment and activation of peripheral blood monocytes are potentially critical regulatory events for the control of pulmonary inflammation. The chemokine monocyte chemoattractant protein (MCP)-1 is a potent chemoattractant for monocytes. MCP-1 is produced by lung epithelial cells during the course of inflammatory lung diseases. In the present study, we examined the effects of a thiazolidinedione (TZD), which is used to improve the insulin resistance of individuals with diabetes mellitus, on MCP-1 expression in a human lung epithelial cell line, A549. MEASUREMENTS AND RESULTS: In A549 cells, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha induced endogenous MCP-1 protein secretion and messenger RNA expression. The TZD inhibited the increase of MCP-1 secretion by IL-1beta and TNF-alpha treatment. The TZD inhibited the expression of MCP-1 messenger RNA with IL-1beta treatment, but not with TNF-alpha treatment. This observation was confirmed by the results of a monocyte chemotactic assay. The transcriptional activity of human MCP-1 promoter in A549 cells paralleled the endogenous messenger RNA expression by cytokines and TZD treatment. CONCLUSIONS: Our findings indicated that the suppression of the expression of MCP-1 could be accomplished by TZD treatment, raising the possibility that TZD may be of therapeutic value in several lung diseases in which MCP-1 plays an important role.
Subject(s)
Chemokine CCL2/antagonists & inhibitors , Interleukin-1/pharmacology , Lung/drug effects , Thiazoles/pharmacology , Thiazolidinediones , Tumor Necrosis Factor-alpha/pharmacology , Adenocarcinoma , Chemokine CCL2/genetics , Gene Expression/drug effects , Humans , Lung Neoplasms , RNA, Messenger/drug effects , RNA, Messenger/genetics , Respiratory Mucosa/drug effects , Tumor Cells, CulturedABSTRACT
A patient with extramedullary crisis from chronic myelogenous leukemia after allogeneic bone marrow transplantation is reported. A pathological neck lymph node observed after transplantation revealed pre-T lymphoblastic phenotype, and the fluorescence in situ hybridization (FISH) analysis showed recipient type sex chromosomes and bcr/abl fusion gene. The cells represented an additional translocation, t(6;8)(q25;q22). No rearrangements of the T-cell receptor (TCR) beta, gamma or delta chain genes were observed. The absence of TCR rearrangement indicated the clonogenic involvement of pluripotent hematopoietic stem cells by Philadelphia chromosome. Bone marrow specimens at that time showed donor type sex chromosomes and no bcr/abl-positive cells by FISH.
Subject(s)
Blast Crisis , Bone Marrow Transplantation , Chromosomes, Human, Pair 6 , Chromosomes, Human, Pair 8 , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Translocation, Genetic , Gene Rearrangement, T-Lymphocyte , Humans , Immunophenotyping , In Situ Hybridization, Fluorescence , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Lymph Nodes/immunology , Male , Middle Aged , Transplantation, HomologousABSTRACT
Bronchial asthma is a clinical syndrome characterized by the reversibility of airway obstruction. Recently it has been suggested that remodeling of the airway causes irreversible airway obstruction which may be responsible for the patient's symptoms. With this background, the purpose of the present study was to assess patients with corticosteroid-dependent asthma by Tc-99m Technegas scintigraphy (Technegas) in both planar and SPECT images. Twelve patients (7 females and 5 males aged 36-72 years with a median age of 60 years: 4 smokers and 8 non-smokers) with oral corticosteroid-dependent asthma were enrolled in this study. Lung ventilation scanning with Technegas in both planar and SPECT images, high-resolution computed tomography, and pulmonary function tests were performed in all patients. The results of Technegas scanning were graded and correlations with other clinical parameters were evaluated. Significant abnormalities were detected by ventilation scintigraphy with Technegas in patients with corticosteroid-dependent bronchial asthma even during remission. Our data demonstrate that airflow obstruction took place in patients with corticosteroid-dependent asthma even during remission. Technegas scanning appears to be a useful radiopharmaceutical for demonstrating airflow obstruction in patients with bronchial asthma.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Asthma/diagnostic imaging , Asthma/drug therapy , Lung/diagnostic imaging , Radiopharmaceuticals , Sodium Pertechnetate Tc 99m , Ventilation-Perfusion Ratio , Adult , Aged , Asthma/physiopathology , Bronchi/pathology , Female , Humans , Lung/pathology , Lung/physiopathology , Male , Middle Aged , Radiopharmaceuticals/pharmacokinetics , Smoking , Sodium Pertechnetate Tc 99m/pharmacokinetics , Tomography, Emission-Computed, Single-PhotonABSTRACT
The chemokine monocyte chemoattractant protein-1 is a potent chemoattractant for monocytes. Monocyte chemoattractant protein-1 is produced by vascular endothelial cells during inflammatory diseases such as atherosclerosis. In this study, we examined the effects of a thiazolidinedione on monocyte chemoattractant protein-1 expression in human vascular endothelial cells. In human vascular endothelial cells, interleukin-1beta and tumor necrosis factor-alpha induced endogenous monocyte chemoattractant protein-1 protein secretion, mRNA expression and promoter activity. The thiazolidinedione inhibited these effects. In summary, our results indicated that the suppression of the expression of monocyte chemoattractant protein-1 can be accomplished by thiazolidinedione treatment, raising the possibility that thiazolidinedione may be of therapeutic value in the treatment of diseases such as atherosclerosis.
Subject(s)
Chemokine CCL2/biosynthesis , Cytokines/pharmacology , Endothelium, Vascular/drug effects , Thiazoles/pharmacology , Thiazolidinediones , Chemokine CCL2/antagonists & inhibitors , Dose-Response Relationship, Drug , Endothelium, Vascular/metabolism , Humans , Interleukin-1/pharmacology , Promoter Regions, Genetic , Pyrimidines/pharmacology , Time Factors , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
The chemokine RANTES is a potent chemoattractant for eosinophils. RANTES is produced by lung epithelial cells during eosinophil-rich inflammatory diseases such as asthma. In this study, we examined the effects of thiazolidinediones (TZD) on RANTES expression in a human lung epithelial cell line, A549. In A549 cells, interleukin-1beta and tumor necrosis factor-alpha induced endogenous RANTES protein secretion, mRNA expression, and promoter activity. The TZD inhibited these effects. Our data indicate that the suppression of the expression of RANTES can be accomplished by TZD treatment, raising the possibility that TZD might be of therapeutic value in diseases such as asthma.
Subject(s)
Chemokine CCL5/genetics , Eosinophils/physiology , Epithelial Cells/metabolism , Gene Expression Regulation/drug effects , Thiazoles/pharmacology , Thiazolidinediones , Cell Line , Chemokine CCL5/biosynthesis , Chemotaxis, Leukocyte/drug effects , Dexamethasone/pharmacology , Eosinophils/drug effects , Epithelial Cells/drug effects , Humans , Hypersensitivity/blood , In Vitro Techniques , Interleukin-1/pharmacology , Luciferases/genetics , Lung/drug effects , Lung/metabolism , Promoter Regions, Genetic/drug effects , Pyrimidines/pharmacology , RNA, Messenger/genetics , Recombinant Proteins/biosynthesis , Transcription, Genetic/drug effects , Transfection , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Although the inhalation of beta2-agonists has frequently been used to relieve acute asthma attacks, the efficacy of anticholinergic agents for acute asthma attacks still remains unclear. This study was designed to compare the inhalation of fenoterol and the inhalation of fenoterol plus oxitropium bromide delivered by a metered-dose inhaler with holding chamber (InspirEase) to relieve acute asthma attacks. To accomplish this, 69 patients who had presented with an acute asthma attack were randomized to receive either fenoterol (1 puff [200 microg/puff] every 1 min for 5 min; total 1000 microg) or fenoterol plus oxitropium bromide (2 puffs [100 microg/puff] every 1 min for 5 min; total 1000 microg). The peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1) values were measured before treatment, and 1, 15, 30, and 60 min after the inhalation therapy. The ratios of improvement, PEF (or FEV1) after treatment divided by PEF (or FEV1) before treatment, were also calculated. Thirty-three patients were evaluated in the combination group and 31 patients were evaluated in the fenoterol group. The PEF value at 60 min after inhalation therapy of the fenoterol plus oxitropium bromide group (261 +/- 18 L/min, mean +/- standard error) was significantly higher compared to that of the fenoterol group (210 +/- 17 L/min). In addition, the ratios of improvement of PEF at 1, 15, 30, and 60 min after inhalation therapy were significantly higher in the fenoterol plus oxitropium bromide group compared with the fenoterol group.
