epidermal-growth-factor and Pulmonary-Disease--Chronic-Obstructive

Chronic obstructive pulmonary disease (COPD) is characterized by chronic obstruction of expiratory flow affecting peripheral airways, associated with chronic bronchitis (mucus hypersecretion with goblet cell and submucosal gland hyperplasia) and emphysema (destruction of airway parenchyma), together with fibrosis and tissue damage, and inflammation of the small airways. Cytokines are extracellular signalling proteins. Increased levels of interleukin (IL)-6, IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and IL-8 have been measured in sputum, with further increases during exacerbations, and the bronchiolar epithelium over-expresses monocyte chemotactic protein (MCP)-1 and IL-8. IL-8 can account for some chemotactic activity of sputum, and sputum IL-8 levels correlate with airway bacterial load and blood myeloperoxidase levels. The expression of chemokines such as regulated on activation, normal T-cell expressed and secreted (RANTES) may underlie the airway eosinophilia observed in some COPD patients. Cytokines may be involved in tissue remodelling. TNF-alpha and IL-1beta stimulate macrophages to produced matrix metalloproteinase-9 (MMP-9), and bronchial epithelial cells to produce extracellular matrix glycoproteins such as tenascin. Increased expression of transforming growth factor-beta (TGFbeta) and of epidermal growth factor (EGF) occurs in the epithelium and submucosal cells of patients with chronic bronchitis. TGFbeta and EGF activate proliferation of fibroblasts, while activation of the EGF receptor leads to mucin gene expression. The cytokine profile seen in chronic obstructive pulmonary disease is different from that observed in asthma. The role of these cytokines needs to be defined and there is a potential for anticytokine therapy in chronic obstructive pulmonary disease.

Topics: Cytokines; Eosinophils; Epidermal Growth Factor; Female; Humans; Inflammation; Interleukin-1; Interleukin-8; Male; Prognosis; Pulmonary Disease, Chronic Obstructive; Sensitivity and Specificity; Severity of Illness Index; Transforming Growth Factor beta

Little is known about the effects of long-term nasal low-flow oxygen (NLFO) on mucus and symptoms and how this variable is affected by dry or cold humidified gas. The aim of this study was to investigate the effects of dry-NLFO and cold bubble humidified-NLFO on nasal mucociliary clearance (MCC), mucus properties, inflammation, and symptoms in subjects with chronic hypoxemia requiring long-term domiciliary oxygen therapy.. Eighteen subjects (mean age, 68 years; 7 male; 66% with COPD) initiating NLFO were randomized to receive dry-NLFO (n = 10) or humidified-NLFO (n = 8). Subjects were assessed at baseline, 12 h, 7 days, 30 days, 12 months, and 24 months by measuring nasal MCC using the saccharin transit test, mucus contact angle (surface tension), inflammation (cells and cytokine concentration in nasal lavage), and symptoms according to the Sino-Nasal Outcome Test-20.. Nasal MCC decreased significantly (40% longer saccharin transit times) and similarly in both groups over the study period. There was a significant association between impaired nasal MCC and decline in lung function. Nasal lavage revealed an increased proportion of macrophages, interleukin-8, and epidermal growth factor concentrations with decreased interleukin-10 during the study. No changes in the proportion of ciliated cells or contact angle were observed. Coughing and sleep symptoms decreased similarly in both groups. There were no outcome differences comparing dry vs cold bubble humidified NLFO.. In subjects receiving chronic NLFO, cold bubble humidification does not adequately humidify inspired oxygen to prevent deterioration of MCC, mucus hydration, and pulmonary function. The unheated bubble humidification performed no better than no humidification.. ClinicalTrials.gov; No.: NCT02515786; URL: www.clinicaltrials.gov.

Topics: Aged; Aged, 80 and over; Bronchiectasis; Cough; Cytokines; Disease Progression; Epidermal Growth Factor; Female; Humans; Humidifiers; Humidity; Hypertension, Pulmonary; Interleukin-10; Interleukin-8; Macrophages; Male; Middle Aged; Mucociliary Clearance; Mucus; Nasal Lavage Fluid; Oxygen Inhalation Therapy; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Respiratory Function Tests; Surface Tension

Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers. Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial. This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.. Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab. Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109). Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.. Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins. This profile was largely independent of smoking status, age, and clinical phenotype. The majority of these associations of serum analytes with COPD are novel findings. Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement. Infliximab did not affect this systemic inflammatory profile.. A robust systemic inflammatory profile was associated with COPD. This profile was generally independent of disease severity. Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.

Topics: Acute-Phase Proteins; Adult; Aged; Anti-Inflammatory Agents; Antibodies, Monoclonal; Brain-Derived Neurotrophic Factor; C-Reactive Protein; CD40 Antigens; Creatine Kinase; Epidermal Growth Factor; Female; Humans; Inflammation; Infliximab; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Tumor Necrosis Factor-alpha

Epidermal growth factor receptor (EGFR) activation is implicated in mucin hypersecretion in chronic obstructive pulmonary disease (COPD).. To investigate the safety and efficacy of an inhaled EGFR antagonist (BIBW 2948) in COPD.. Multicenter, double-blind, placebo-controlled trial of 4 weeks of treatment with two doses of BIBW 2948 (15 and 30 mg twice a day) on safety and mucin-related outcomes in 48 patients with COPD. The effect of BIBW 2948 on EGFR activation in airway epithelial cells was assessed using an ex vivo assay. Efficacy measures included the volume of mucin in the airway epithelium (Vs mu,bala) in bronchial biopsies and the expression of mucin genes in bronchial brushings.. Inhaled BIBW 2948 induced a dose-related inhibition of EGFR internalization (reflecting decreased EGFR activation) in epithelial cells from treated subjects. However, BIBW 2948 was associated with a dose-related increase in adverse events, including reversible liver enzyme elevation (n = 2), and reduction in FEV(1). The changes in mucin stores and mucin gene expression were not significantly different in the pooled BIBW 2948 group versus placebo (volume of mucin per surface area of basal lamina = 0.22 +/- 7.11 vs. 0.47 +/- 8.06 microm(3)/microm(2); P = 0.93). However, in the 30 mg twice a day group, the reduction in epithelial mucin stores was greatest in subjects with the greatest degree of EGFR inhibition (Pearson r = 0.98; 95% confidence interval, 0.71-0.99).. Four-week treatment with BIBW 2948 did not significantly decrease epithelial mucin stores and was poorly tolerated in patients with COPD. Ex vivo analyses suggest that higher doses may be more effective at both EGFR inhibition and decreases in mucin stores but that adverse events should be expected. Clinical trial registered with www.clinicaltrials.gov (NCT00423137).

Topics: Administration, Inhalation; Adult; Aged; Bronchoscopy; Double-Blind Method; Epidermal Growth Factor; ErbB Receptors; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Mucins; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

Aryl hydrocarbon receptor (AHR) genomic pathway has been well-characterized in a number of respiratory diseases. In addition, the cytoplasmic AHR protein may act as an adaptor of E3 ubiquitin ligase. In this study, the physiological functions of AHR that regulate cell proliferation were explored using the CRISPR/Cas9 system. The doubling-time of the AHR-KO clones of A549 and BEAS-2B was observed to be prolonged. The attenuation of proliferation potential was strongly associated with either the induction of p27

Topics: A549 Cells; ADAM17 Protein; Animals; Cell Cycle; Cell Cycle Checkpoints; Cell Proliferation; Clone Cells; Epidermal Growth Factor; ErbB Receptors; Humans; Lung; Membrane Glycoproteins; Mice, Inbred C57BL; Mice, Knockout; Mitogens; Proteolysis; Pulmonary Disease, Chronic Obstructive; Receptors, Aryl Hydrocarbon; Signal Transduction; Up-Regulation

A low quadriceps slow-twitch (ST), oxidative (relative to fast-twitch) fiber proportion is prevalent in chronic diseases such Chronic Obstructive Pulmonary Disease (COPD) and is associated with exercise limitation and poor outcomes. Benefits of an increased ST fiber proportion are demonstrated in genetically modified animals. Pathway analysis of published data of differentially expressed genes in mouse ST and FT fibers, mining of our microarray data and a qPCR analysis of quadriceps specimens from COPD patients and controls were performed. ST markers were quantified in C2C12 myotubes with EGF-neutralizing antibody, EGFR inhibitor or an EGFR-silencing RNA added. A zebrafish egfra mutant was generated by genome editing and ST fibers counted. EGF signaling was (negatively) associated with the ST muscle phenotype in mice and humans, and muscle EGF transcript levels were raised in COPD. In C2C12 myotubes, EGFR inhibition/silencing increased ST, including mitochondrial, markers. In zebrafish, egfra depletion increased ST fibers and mitochondrial content. EGF is negatively associated with ST muscle phenotype in mice, healthy humans and COPD patients. EGFR blockade promotes the ST phenotype in myotubes and zebrafish embryos. EGF signaling suppresses the ST phenotype, therefore EGFR inhibitors may be potential treatments for COPD-related muscle ST fiber loss.

Topics: Aged; Animals; Case-Control Studies; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Locomotion; Male; Mice; Middle Aged; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Oxidation-Reduction; Phenotype; Protein Kinase Inhibitors; Pulmonary Disease, Chronic Obstructive; RNA, Messenger; Zebrafish

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by different phenotypes with either bronchial airways alterations or emphysema prevailing. As blood biomarkers could be clinically useful for COPD stratification, we aimed at investigating the levels of blood biomarkers in COPD patients differentiated by phenotype: prevalent chronic airway disease versus emphysema.. In 23 COPD patients with prevalent airway disease (COPD-B), 22 COPD patients with prevalent emphysema (COPD-E), 9 control smokers (CSs), and 18 control nonsmokers (CNSs), we analyzed the expression levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, epidermal growth factor (EGF), monocyte chemotactic protein (MCP)-1, and vascular endothelial growth factor by enzyme-linked immunosorbent assay in plasma/serum; glutathione peroxidase and superoxide dismutase (SOD)-1 by immunochemical kits in plasma; and free F2-isoprostanes (F2-IsoPs) by gas chromatography in plasma.. F2-IsoPs level was increased in COPD-B and COPD-E compared with CSs and CNSs; in addition, CS showed higher levels than CNSs; SOD1 level was lower in COPD-B and COPD-E than that in CNSs. Interestingly, MCP-1 level was higher only in COPD-E versus CSs and CNSs; EGF and IL-8 levels were higher in COPD-B and COPD-E versus CNSs; IL-6 level was increased in all three smoking groups (COPD-B, COPD-E, and CSs) versus CNS; IFN-γ and IL-1α levels were higher in CSs than in CNSs; and IL-1α level was also higher in CSs versus COPD-B and COPD-E. In all subjects, F2-IsoPs level correlated positively and significantly with MCP-1, IL-2, IL-1β, IFN-γ, and TNF-α and negatively with SOD1. When correlations were restricted to COPD-E and COPD-B groups, F2-IsoPs maintained the positive associations with IFN-γ, TNF-α, and IL-2.. We did not find any specific blood biomarkers that could differentiate COPD patients with prevalent airway disease from those with prevalent emphysema. The MCP-1 increase in COPD-E, associated with the imbalance of oxidant/antioxidant markers, may play a role in inducing emphysema.

Topics: Aged; Biomarkers; Case-Control Studies; Chemokine CCL2; Epidermal Growth Factor; F2-Isoprostanes; Female; Glutathione Peroxidase; Humans; Interferon-gamma; Interleukins; Male; Non-Smokers; Phenotype; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Smokers; Smoking; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung and systemic inflammation as well as airway goblet cell hyperplasia (GCH). Mucin production is activated in part by stimulation of the epidermal growth factor (EGF) receptor pathway through neutrophils and macrophages. How circulating cytokine levels relate to GCH is not clear.. We performed phlebotomy and bronchoscopy on 25 subjects (six nonsmokers, 11 healthy smokers, and eight COPD subjects FEV1 30-60 %). Six endobronchial biopsies per subject were performed. GCH was measured by measuring mucin volume density (MVD) using stereological techniques on periodic acid fast-Schiff stained samples. We measured the levels of chemokines CXCL8/IL-8, CCL2/MCP-1, CCL7/MCP-3, CCL22/MCD, CCL3/MIP-1α, and CCL4/MIP-1β, and the cytokines IL-1, IL-4, IL-6, IL-9, IL-17, EGF, and vascular endothelial growth factor (VEGF). Differences between groups were assessed using one-way ANOVA, t test, or Chi squared test. Post hoc tests after ANOVA were performed using Bonferroni correction.. MVD was highest in healthy smokers (27.78 ± 10.24 μL/mm(2)) compared to COPD subjects (16.82 ± 16.29 μL/mm(2), p = 0.216) and nonsmokers (3.42 ± 3.07 μL/mm(2), p < 0.0001). Plasma CXCL8 was highest in healthy smokers (11.05 ± 8.92 pg/mL) compared to nonsmokers (1.20 ± 21.92 pg/mL, p = 0.047) and COPD subjects (6.01 ± 5.90 pg/mL, p = 0.366). CCL22 and CCL4 followed the same trends. There were no significant differences in the other cytokines measured. When the subjects were divided into current smokers (healthy smokers and COPD current smokers) and non/ex-smokers (nonsmokers and COPD ex-smokers), plasma CXCL8, CCL22, CCL4, and MVD were greater in current smokers. No differences in other cytokines were seen. Plasma CXCL8 moderately correlated with MVD (r = 0.552, p = 0.003).. In this small cohort, circulating levels of the chemokines CXCL8, CCL4, and CCL22, as well as MVD, attain the highest levels in healthy smokers compared to nonsmokers and COPD subjects. These findings seem to be driven by current smoking and are independent of airflow obstruction.. These data suggest that smoking upregulates a systemic pattern of neutrophil and macrophage chemoattractant expression, and this correlates significantly with the development of goblet cell hyperplasia.

Topics: Adult; Aged; Case-Control Studies; Chemokine CCL2; Chemokine CCL22; Chemokine CCL3; Chemokine CCL4; Chemokine CCL7; Chemokines; Cytokines; Epidermal Growth Factor; Female; Goblet Cells; Humans; Hyperplasia; Interleukin-1; Interleukin-17; Interleukin-4; Interleukin-6; Interleukin-8; Interleukin-9; Lung; Male; Middle Aged; Mucins; Pulmonary Disease, Chronic Obstructive; Smoking; Vascular Endothelial Growth Factor A

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of morbidity and mortality in the industrialized and in the developing countries. It is believe, at least in part, that some of the structural changes that occur in COPD would be a result of epidermal growth factors (EGFs) and their receptors. Therefore, our study aims was to examine the expression patterns of EGF and their receptors (EGFR1 and c-erbB2) in the bronchial mucosa from the biopsy specimens harvested from smoking and non-smoking CB patients, compared with their expression in normal controls. The statistical analysis proved that for both EGF and EGFR1 reactivity were significant correlation with smoking status and FEV1% scores. Thus, we found that the highest levels of its expression were recorded in smoker CB patients with higher FEV1% scores. Regarding cellular localization and staining pattern, we noticed a cytoplasmic and nuclear immunostaining for EGF in bronchial epithelium both for control and CB subjects at the level of basal and ciliated cells. For the receptors, reactions were at the membrane level especially at the lower lateral junctions between ciliated cells and their junctions with basal cells. This reactivity proved the pathogenic implication of the EGF and their receptors in patients with CB and suggests that blockade of the EGFR pathway can be an alternative successful therapy.

Topics: Aged; Animals; Bronchitis, Chronic; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Receptor, ErbB-2

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by permanent and progressive airway obstruction. Cigarette smoking is the main cause responsible for COPD although only 15 to 25 % of smokers develop COPD. Mechanisms underlying COPD pathogenesis are not fully understood. Structural abnormalities in small airways (bronchioles < 2mm in diameter) are the main determinants of airway obstruction; obstruction of these bronchioles is related to increase in airway wall thickness (associated with peribronchiolar fibrosis) and to plugging by mucus exudates. Alveolar wall destruction (emphysema) also contributes to airway obstruction and to gas exchange abnormalities. Current knowledge related to molecular and cellular mechanisms responsible for these structural modifications are reviewed.

Topics: Bronchi; Disease Progression; Emphysema; Epidermal Growth Factor; ErbB Receptors; Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Smoking

Smoking may affect epithelial repair and differentiation differentially in smokers with and without chronic obstructive pulmonary disease (COPD). We hypothesized that epithelial repair is disturbed in patients with COPD owing to higher expression of epidermal growth factor (EGF)-like factors and/or receptors. We studied epithelial expression of EGF, transforming growth factor a, amphiregulin, heregulin (HRG), betacellulin (BTC), and their receptors, EGFR, HER-2, and HER-3, by immunohistochemical analysis in resected bronchial tissue from 20 subjects with (forced expiratory volume in 1 second [FEV(1)] <75% of predicted value) and 18 without (FEV(1) >85% predicted value) COPD. All subjects underwent surgery for lung cancer. The proportion of intact, damaged, goblet, or squamous metaplastic epithelium was similar in subjects with and without COPD. Regardless of smoking status, HRG expression was higher in intact epithelium of patients with COPD than in those without. Subgroup analysis showed higher EGFR expression in intact epithelium (1.4 times; P pound .04) and higher EGF, BTC, and HRG expression in damaged epithelium (1.4-1.8 times; P

Topics: Adult; Aged; Animals; Bronchi; Epidermal Growth Factor; Epithelium; ErbB Receptors; Female; Humans; Immunohistochemistry; Male; Mice; Middle Aged; Pulmonary Disease, Chronic Obstructive; Rabbits

Airway smooth muscle (ASM) hypertrophy and hyperplasia, important pathological features in chronic severe asthma, likely contribute to irreversible airflow obstruction. Despite considerable research effort, the precise cellular mechanisms that modulate ASM growth remain unknown. Src, a nonreceptor tyrosine kinase proto-oncogene, reportedly modulates cell proliferative responses to growth factors, contractile agonists, and inflammatory mediators. Here, we show that Src activation is required for human ASM mitogenesis and motility. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and thrombin induce rapid activation of Src, and inhibition of Src induces a concentration-dependent abrogation of PDGF-, EGF-, and thrombin-induced ASM cell proliferation. Src immunoprecipitates had associated phosphatidylinositol 3-kinase, or PI3K, activation in response to PDGF and thrombin but not EGF. Further, Src activation is both necessary and sufficient for the stimulation of DNA synthesis as demonstrated by dominant negative Src inhibition of PDGF-, EGF-, and thrombin-induced DNA synthesis. Human ASM cell migration was also attenuated by transfection of cells with dominant negative Src. Further, expression of constitutively active Src promoted cell migration. Collectively, these data demonstrate that Src modulates human ASM cell proliferation and migration, suggesting that Src may play an important role in promoting ASM cell growth and migration that occur in airway remodeling found in asthma and chronic obstructive pulmonary disease, or COPD.

Topics: Asthma; Cell Division; Cell Movement; Cells, Cultured; DNA; Enzyme Activation; Enzyme Inhibitors; Epidermal Growth Factor; Gene Expression; Humans; Immunoblotting; Muscle, Smooth; Mutation; Phosphatidylinositol 3-Kinases; Platelet-Derived Growth Factor; Proto-Oncogene Mas; Pulmonary Disease, Chronic Obstructive; Recombinant Fusion Proteins; src-Family Kinases; Thrombin; Trachea; Transfection

Topics: Air Pollutants; Allergens; Animals; Epidermal Growth Factor; Epithelium; ErbB Receptors; Expectorants; Humans; Mucus; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases

To study the pathological features of the smooth muscles and collagen in small airways of the COPD rat models and their roles in the airway obstruction, to evaluate the relationship between TGF-beta(1), EGF and bFGF and the airway wall remodeling.. Rat COPD model (model group) was established by intratracheal instillation of lipopolysaccharide (LPS 200 microgram/200 microL) twice and exposure to cigarette smoke daily. Drug intervention groups received either daily inhalation of budesonide, ipratropine or heparin respectively, starting on the 8 th day or TGF-beta(1) monoclonal antibody (TB21) 0.5 mg twice (6 th and 19 th day) via the tail veinous injection. At the end of four weeks, the thickness of the smooth muscles and collagen in bronchi and pulmonary arteriole wall were measured by means of image analyzer (CMIAS). Expression and localization of the 3 growth factors were observed in trachea, bronchi and lung tissues by immunohistochemistry and in situ hybridization. The levels of PC III, Ln and HA in the serum and BALF were determined by the RIA method.. Significant thickening of the smooth muscles and collagen were found in the bronchi and pulmonary arterioles of the model group in comparison with those of the control group. There was significant decrease in the thickness of the collagen and smooth muscles in the small airways in TB21 group and heparin group. Statistically negative relationships were shown between the thickness of either smooth muscles or collagen in the small airways and FEV(0.3) (all P < 0.05). The levels of PC III, Ln and HA in COPD rat models were higher than those of control groups to varying extent. Expressions of TGF-beta(1), EGF and bFGF in the epithelial cells of bronchi, endothelial cells of pulmonary arterioles and in the macrophages of the model group were significantly higher than those of control group. The above mentioned parameters were reduced in different extent in drug intervention groups, in particular, the smooth muscles thickness in heparin group and the collagen thickness in TB21 group were significantly decreased compared to the model group.. Thickening of smooth muscles and collagen in the bronchi constitutes the fundamental pathology of airway remodeling in the rat COPD model. The excessive depositions of ECM are important characteristics of COPD. TGF-beta(1), EGF and bFGF may play an important role in the airway wall as well as pulmonary arteriole remodeling. The intervention against TGF-beta(1) and long term inhalation of heparin may be of use in the inhibition of airway remodeling in COPD.

Topics: Animals; Arterioles; Bronchi; Bronchoalveolar Lavage Fluid; Collagen Type III; Disease Models, Animal; Epidermal Growth Factor; Fibroblast Growth Factor 2; Lung; Male; Muscle, Smooth, Vascular; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Wistar; Transforming Growth Factor beta; Transforming Growth Factor beta1

To evaluate the expression and distribution of transforming growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) in the lung tissue of chronic obstructive pulmonary (COPD) rat models and the relationship between these growth factors and the airway wall remodeling. The effects of drugs on them were also investigated.. The COPD rat model (model group) was established by intratracheal instillation of lipopolysaccharide twice and daily exposure to cigarette smoking. Drug intervention groups received daily inhalation of heparin since the second week and TGF-beta1 monoclonal antibody (TB21) 0.5 mg twice through the tail veins. At the end of four weeks, the thickness of the smooth muscle and collagen in bronchi and pulmonary arterioles were measured by computer image analyzer, also the protein and gene relative content of these growth factors as well as the effects of drugs on them were observed.. There was a significant increase in the smooth muscle and collagen thickness in the bronchi and pulmonary arterioles of the model group in comparison with that of the control group (P < 0.01), the relative contents for TGF-beta1, EGF and bFGF in the epithelial cells of the bronchi, endothelial cells of the pulmonary arterioles and alveolar macrophages of the model group were significantly higher than those of control group (P < 0.001 approximately 0.05). The relative content for TGF-beta1 in TB21 group was significantly lower than that of model group (P < 0.01). These were statistical positive relationships between the smooth muscle e thickness of bronchi and the relative contents for TGF-beta1, EGF and bFGF in the epithelial cells, between the collagen thickness of the bronchi and the relative content for TGF-beta1, between the smooth muscle thickness of the pulmonary arterioles and the relative content for TGF-beta1 and EGF in the endothelial cells (P < 0.05 approximately 0.01).. TGF-beta1, EGF and bFGF may play an important role in the airway wall and pulmonary arteriole structure remodeling in COPD, the intervention against TGF-beta1 and long term inhalation of heparin mat be helpful for the inhibition of airway wall remodeling in human COPD and worth of further observation.

Topics: Animals; Bronchi; Disease Models, Animal; Epidermal Growth Factor; Fibroblast Growth Factor 2; Heparin; Lipopolysaccharides; Male; Muscle, Smooth, Vascular; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Wistar; Transforming Growth Factor beta