Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032273 (pneumoconiosis)
 1,578 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following our previous demonstration of cytokine secretion by alveolar macrophages (AM) from coal miners and from patients with coal workers' pneumoconiosis, we investigated the effect of in vitro exposure to coal dust and to its silica content on tumor necrosis factor-alpha (TNF), interleukin (IL)-1 beta, and IL-6 production by normal human AM. TNF and IL-1 beta concentrations were estimated by a specific radioimmunoassay, while IL-6 levels were evaluated by the proliferation of 7TD1 cells. After 24-h culture, coal dust triggered a significant release of TNF and IL-6 at the dose of 0.1 mg/ml and more obviously at 1 mg/ml in comparison with titanium dioxide (TiO2), used as a biologically inert control dust (with 1 mg/ml of dust: 3,526 +/- 3,509 versus 330 +/- 138 pg TNF/ml and 224 +/- 74 versus 72 +/- 34 U IL-6/ml, respectively; P less than 0.01 in both cases). After 3-h culture, a significant TNF secretion as well as an increased TNF mRNA expression were also detected for AM stimulated by coal dust at variance with TiO2. In contrast, no modification of IL-1 beta concentration could be evidenced in AM exposed to coal dust, although we detected an increased expression of specific mRNA expression. In order to define the role of silica among the main components of coal dust in AM activation, we evaluated the effect of silica (alpha-quartz, 30 micrograms/ml, which is the concentration and the type of silica present in our coal dust) alone or mixed with TiO2 (1 mg/ml) on monokine production.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Production of tumor necrosis factor-alpha and interleukin-6 by human alveolar macrophages exposed in vitro to coal mine dust. 165 62

This review summarizes recent research bearing on the role played by cells of the immune system in the development of pneumoconiosis. Findings related to the cellular and humoral immune responses to silica and asbestos are highlighted. Experimental results from humans and animal models are integrated into our current understandings of cellular and cytokine-mediated pathways leading to the generation of immune responses that may contribute to fibrogenesis and fibrosis. Potential mechanisms leading to the generation of an immune response by particulates are discussed, together with the indirect effects of particulates on fibroblasts by way of the cytokine network in the lung. Finally, suggestions are given for future research to help further elucidate the relationships between the cellular components of the immune system of the lung and the fibroblast that lead to fibrosis.
 ...
PMID:Immunologic aspects of pneumoconiosis. 165 88

Communication between cells determines the steady-state composition of the lung in health and becomes a critical determinant of outcome in pathologic processes resulting in anatomic remodeling. This review presents the evolving concepts of the biology of cytokines (also known as peptide growth factors or biological response modifiers) in maintaining normal tissue growth and homeostasis. How these extracellular signaling proteins are involved in such pathologic disorders as spontaneous pulmonary fibrosis, sarcoidosis, pneumoconiosis, and the evolution and recovery from acute lung injury is also discussed. During the past decade the cytokines have come to the fore as important multifunctional mediators of cell behavior and cell-cell communication. A wide range of cellular responses are influenced or triggered when cytokines interact with cells. These include mitosis, chemotaxis, angiogenesis, cytoskeleton arrangement, immunomodulation, and extracellular matrix production. Cytokines influence cell behavior by binding to specific high affinity surface receptors on target cells. These receptors are linked in turn at the cell membrane to a complex array of intracellular signaling pathways. Individual cytokines may inhibit as well as promote cellular functions such as mitosis and thereby play a critical role in homeostasis of normal tissue elements. Hence, cytokines are intimately involved in normal tissue homeostasis as well as in processes eventuating in growth and remodeling. All cells produce and secrete cytokines at some time during their life. Each cytokine is capable of modulating more than one cellular function. Although produced by a variety of cell types, the triggers that induce a specific cytokine to be produced differ between cells. Many of the cytokines share regions of homologous nucleic acid sequences, suggesting that they are members of larger gene families. Given that tissues and cells are exposed to complex cytokine mixtures rather than to individual cytokines, recent attention has turned to understanding how cytokines interact. The combined effects of cytokine mixtures have proved to be both complex and unpredictable based on knowledge of the separate actions of the individual cytokines involved. In studies of the role of cytokines in lung disease, early research attention has focused on those cytokines released by alveolar macrophages (the so-called macrophage-derived growth factors). However, structural cells as well as immune effector cells of the lung are capable of cytokine production and release. The cytokines receiving the most attention to date in relation to pulmonary diseases include platelet-derived growth factor (PDGF), interleukin-1 (IL-1), transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), insulinlike growth factor I (IGF-I), and, most recently, interleukin-6 (IL-6).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Cytokines of the lung. 224 Aug 51

The aim of this study was to compare the secretion of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by alveolar macrophages (AMs) harvested from patients with coal worker's pneumoconiosis (CWP) and control subjects. We observed higher levels of spontaneous TNF alpha and IL-1 secretion by AMs from patients with CWP than in those from healthy controls. We did not find any significant difference between the two groups in the incidence of simple pneumoconiosis and progressive massive fibrosis. In the group of coal miners without radiologic signs of pneumoconiosis, we found high levels of both cytokines in a subgroup of subjects still exposed to the mineral dust but not in the subgroup of subjects removed from exposure. These results indicate that AMs are involved in chronic lung inflammatory reactions to mineral dusts, partly by way of cytokine secretion. Moreover, cytokine secretion by AMs appears to be an early event that is detectable at the moment of mineral dust exposure. The results open new perspectives in the study of the mechanisms leading to CWP.
 ...
PMID:Abnormal secretion of interleukin-1 and tumor necrosis factor alpha by alveolar macrophages in coal worker's pneumoconiosis: comparison between simple pneumoconiosis and progressive massive fibrosis. 230 49

Exposure to coal-mine dust leads to coal workers' pneumoconiosis (CWP), characterized by the development of a perifocal and progressive fibrotic reaction. In order to confirm their in vivo participation in the pathogenesis of CWP, the expression of tumor necrosis factor (TNF) and interleukin-6 (IL-6) was evaluated in bronchoalveolar lavage (BAL) specimens collected from 12 patients with simple pneumoconiosis (SP) and six with progressive massive fibrosis (PMF), and in pulmonary tissue from one patient with SP and three with PMF. Expression of TNF and IL-6 was assessed using both in situ hybridization and immunohistochemistry. The number of positive cells found in BALF was significantly higher for patients with PMF (TNF = 55 +/- 6%; IL-6 = 46 +/- 12.8%) than for those with SP (TNF = 34 +/- 11.6%; IL-6 = 26 +/- 10.2%) or normal controls (TNF = 15 +/- 5.5%; IL-6 = 13.3 +/- 6%), and was correlated with cytokine concentrations in supernatants from alveolar macrophages (AM). In lung biopsies, the expression of messenger ribonucleic acid (mRNA) for TNF was associated with the presence of coal dust and was limited to lung macrophages; mRNA for IL-6 was detected in mononuclear phagocytes but also in other types of cells such as endothelial cells. Monokine synthesis was confirmed by immunohistochemistry. These data confirm that TNF and IL-6 production is increased in the lungs of pneumoconiotic patients. Moreover TNF and IL-6 expression was associated with the presence of coalmine dust particles, suggesting a direct role of mineral particles in the cytokine production and development of pneumoconiotic lesions in CWP.
 ...
PMID:Secretion and mRNA expression of TNF alpha and IL-6 in the lungs of pneumoconiosis patients. 759 37

The alveolar macrophage (AM) is a critically important cell playing a prominent role in lung inflammation via the production of oxygen radicals, enzymes, arachidonic acid metabolites, and also a large panel of cytokines. Among interstitial lung disorders, silicosis and coal workers' pneumoconiosis (CWP) are the most widespread fibrotic lung diseases. Although their pathophysiology remains incompletely understood, several lines of evidence suggest the participation of cytokines produced by AMs at least in the initiation of the alveolitis. In vitro exposure of AMs (obtained from healthy subjects) to coal dust particles triggered a significant release of tumour necrosis factor (TNF) and interleukin-6, by comparison with titanium dioxide used as a biologically inert control dust. Moreover, it appeared that coal mine dust was more aggressive than similar concentrations of pure silica, suggesting that cytokine secretion induced by coal mine dust was not exclusively related to the presence of silica but resulted from a complex interaction between the different components. In silicosis and CWP, bronchoalveolar lavage showed a large influx of mononuclear phagocytes, with an increased spontaneous production of oxidants, fibronectin, neutrophil chemotactic factor, and also of interleukin-6 and TNF-alpha. This spontaneous cytokine release was associated with an increased cytokine messenger ribonucleic acid (mRNA) expression in the lungs of coal miners.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis. 765 59

Cytokines are widely involved in physiologic as well as immunoinflammatory and fibrosing processes of the lung. The aim of this work was to study, by bronchoalveolar lavage, two groups of human interstitial lung diseases (ILD) with fibrosing propensity (ie, idiopathic pulmonary fibrosis [IPF], n = 10; and coal worker's pneumoconiosis [CWP], n = 15). Patients were compared with nonsmoker control subjects (n = 20). Cellularity, proteins, and phospholipids were determined in the alveolar fluids. In addition, two cytokines (interleukin-6 [IL-6] and interferon-gamma [IFN-gamma]), which are presumed to possess respective antifibrotic and profibrotic activities, were measured in the respiratory tract. Compared with control subjects, IPF and simple CWP showed alveolar hypercellularity (p < 0.05) and relative lymphocytosis (p < 0.05). Both exhibited increased alveolar permeability (ie, increased albumin/urea ratio, p < 0.05), with enhanced IL-6 and decreased IFN-gamma in the alveolar spaces (p < 0.05). On the other hand, IPF displayed an associated polymorphonuclear alveolitis, enhanced alveolar epithelial lining fluid (AELF) volume and low surfactant phospholipid levels (p < 0.05 vs control), whereas simple CWP shared an exclusive lymphocytosis, normal AELF volume, and a surfactant lipid overflow (p < 0.05 vs control). Relationships among all of these parameters were found only between alveolar cellularity, neutrophils and IL-6 levels in the AELF of IPF (respectively, r = 0.85, p = 0.0009, and r = 0.89, p = 0.0006). In summary, common alterations of cellular and cytokine turnover were observed in IPF and simple CWP and may reflect activity of the antifibrotic fight in these diseased lungs. Surfactant phospholipid levels are likely to represent a specific disturbance among IPF and CWP, but no clear relationship with respect to the other parameters could be established for explaining the difference in time course outcome.
 ...
PMID:Interleukin-6, interferon-gamma, and phospholipid levels in the alveolar lining fluid of human lungs. Profiles in coal worker's pneumoconiosis and idiopathic pulmonary fibrosis. 777 11

Fibrosis is a disorder characterized by a qualitative and quantitative alteration of the deposition of extracellular matrix with accumulation of mesenchymal cells in replacement of normal tissue. The sequence of events leading to fibrosis of an organ involves the subsequent processes of injury with inflammation and disruption of the normal tissue architecture, followed by tissue repair with accumulation of mesenchymal cells in this area. A similar sequence of events occurs in wound healing with formation of normal, limited and transient granulation tissue, while in fibrosis, a maladaptive repair leads to an extensive, exaggerated process with functional impairment. Inflammatory cells (mainly mononuclear phagocytes), platelets, endothelial cells, and type II pneumocytes play a direct and indirect role in tissue injury and repair. The evaluation of several human fibrotic lung diseases, five diffuse (idiopathic pulmonary fibrosis (IPF); adult respiratory distress syndrome (ARDS); coal workers' pneumoconiosis (CWP); Hermansky-Pudlak syndrome (HPS); systemic sclerosis (SS)) and two focal (tumour stroma in lung cancer; and obliterative bronchiolitis (OB) after lung transplantation), has shown that several cytokines participate in the local injury and inflammatory reaction (interleukin-1 (IL-1), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor-alpha (TNF-alpha)), while other cytokines are involved in tissue repair and fibrosis (platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta), and basic-fibroblast growth factor (b-FGF)). A better understanding of the cytokines and cytokine networks involved in lung fibrosis leads to the possibility of new therapeutic approaches.
 ...
PMID:The role of cytokines in human lung fibrosis. 868 Mar 82

Pneumoconiosis that pursues a chronic course may result from repeated injury and repair caused by dust particles that remain in the lungs, leading to fibrosis. We will introduce in vivo studies concerning these processes using animals exposed to man-made mineral fibers and asbestos. We will report on whether there are developmental changes with the mineral fiber and animal model in proinflammatory cytokine, chemokine, free radicals, proteinase and other genes that lead to injury, as well as in genes that effect repair such as growth factor, and we will also report on the effects of surfactant protein and clara cell secretory protein on fibrosis.
 ...
PMID:In vivo studies of man-made mineral fibers--fibrosis-related factors. 1134 39

The aim of this study was to investigate whether systemic tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors (p55, p75), interleukin 6 (IL-6), and soluble IL-6 receptor could be markers of biological activities of coal workers' pneumoconiosis (CWP). The study population was composed of 182 Chinese retired coal miners who had similar dust exposure histories. Among them, 71 were cases with CWP and 111 were controls. Chest radiographs were classified according to International Labour Organization Criteria (ILO, 1980). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Serum concentrations of TNF-alpha, TNF-alpha receptors (p55, p75), IL-6, and IL-6 receptor were measured by ELISA techniques. Mean serum levels of p55, p75 and IL-6 were significantly higher in cases than in controls (P < or = 0.01 for each comparison by crude analyses). Results from logistic regression models, adjusted for age, dust exposure variables, and smoking habits, found similar associations between soluble p55 and p75 levels and the presence of CWP. Linear regression analysis revealed that CWP radiographic stage (by ILO criteria) was significantly correlated with the individual serum concentrations of p55, p75 and IL-6. Serum concentrations of all measured cytokines were notcorrelated to age, dust exposure, or smoking, but there were correlations between soluble p75 and p55 levels, and between p75 and IL-6 levels. The results of this study suggest that serum levels of TNF receptors and IL-6 are associated with the fibrotic process of CWP and serum cytokine levels may be correlated with the severity of CWP.
 ...
PMID:Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and their soluble receptors in coal workers' pneumoconiosis. 1241 84


1 2 Next >>