Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary fibrosis corresponds to an accumulation of collagens and other proteins of the extracellular matrix in the interstitium and alveoli. Biochemical and cellular mechanisms of pulmonary fibrogenesis remain poorly understood. The cells of the alveolitis (macrophages, lymphocytes and neutrophils) play a key role in producing the factors which regulate the proliferation, chemotactism and secretory activity of the fibroblasts. Amongst these factors the cytokines (interleukins, interferons and growth factors) play a definite but very complex role. Certain cytokines stimulate in vitro the attraction and activation of cells of the alveolitis, as well as the multiplication, migration and secretory activity of fibroblasts. The following cytokines are involved: tumour necrosis factor alpha: (TNF alpha), interleukin 1 (IL-1), interleukin 6 (IL-6) interleukin 8 (IL-8) transforming growth factor beta (TGF beta), platelet derived growth factor (PDGF), insulin like growth factor 1 (IGF-1), fibronectin, monocyte chemotactic protein 1: (MCP-1). Other cytokines, principally the interferons (of alpha, beta or gamma type: IFN alpha, IFN beta, IFN gamma) inhibit in vitro and in vivo the proliferation and the production of collagen by fibroblasts. During the course of human pulmonary fibrosis or in experimental situations, the majority of the cytokines mentioned above are produced in excess in the lung. Without doubt they play an important role in the pathogenesis of fibrosis, even if it is not yet very well known how they interact and contribute in vitro to the process of fibrogenesis. Certain cytokines potentially regulating in the fibrosis are yet to be identified. In the future the use of cytokines and of their inhibitors will perhaps provide new therapies in pulmonary fibrosis.
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PMID:[Cytokines and pulmonary fibroses]. 768 79

Studies have indicated that soluble products, including chemotactic factors, released by activated lung macrophages and fibroblasts are critical mediators in the pathogenesis of asbestos-induced pulmonary fibrosis. We provide evidence that mediators produced by lung epithelial cells in response to asbestos may also contribute to lung disease. In the present study, the carcinogenic and fibrogenic fibers, chrysotile and crocidolite asbestos, were shown to directly stimulate the human pulmonary type-II epithelial cell line, A549, and to a lesser degree primary human bronchial epithelial cells, to elicit the chemotactic cytokine IL-8 in the absence of endogenous stimuli such as IL-1 and TNF. That the membrane signaling events responsible for asbestos-induced IL-8 production are distinct from those responsible for IL-8 induction by cytokines was confirmed by using membrane-stabilizing agents and protein synthesis inhibitors. Stimulation was not observed with nonfibrogenic fibers, wollastonite and titanium dioxide, and was the direct result of asbestos-induced initiation of transcription. Asbestos failed to stimulate the release of TNF, IL-1 beta, or monocyte chemoattractant protein-1 in A549 or primary bronchial epithelial cells, indicating that cytokine secretion by asbestos is highly selective. However, a slight release of IL-1 alpha, probably preformed, was released in human bronchial epithelial cells. These data suggest that epithelial cells may, in addition to macrophages and fibroblasts, be an important effector cell in the immunopathogenesis of asbestos-associated diseases and in particular, in the neutrophilic infiltration that is commonly observed after asbestos exposure.
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PMID:Asbestos stimulates IL-8 production from human lung epithelial cells. 808 96

Paraquat (PQ) is a herbicide which is highly pneumotoxic by generating reactive oxygen intermediates (ROI). Pro-inflammatory cytokines, particularly IL-1 and TNF, have been implicated in some ROI-mediated pathologies, including bleomycin toxicity and ischaemia/reperfusion injury. We have studied the effect of PQ on the expression of the neutrophil chemotactic cytokine, IL-8, by human peripheral blood mononuclear cells (PBMC). While almost no IL-8 mRNA was detected in unstimulated cells, PQ (100 microM) induced high mRNA expression with a maximum at 24 h of incubation. While PQ did stimulate the appearance of IL-8 mRNA, no significant production of IL-8 protein was detected. However, PQ potentiated the production of IL-8 in the presence of 1 ng/ml of endotoxin (lipopolysaccharide, LPS). This was paralleled by an increased production of chemotactic activity for neutrophils, indicating that the IL-8 was actually bioactive. Stimulation of IL-8 mRNA by PQ was suppressed by IL-4 and by free radical scavengers (dimethylsulfoxide, mannitol). Increased IL-8 expression by PQ was also observed in the human pulmonary epithelial cell line A549 indicating that the effect of PQ was not specific for PBMC. These findings suggest that IL-8 might be involved in the pulmonary effects of PQ and that its production might be stimulated following an oxidative insult, and might clarify the pathogenetic mechanisms of adult respiratory distress syndrome (ARDS) or oxidant-induced pulmonary fibrosis.
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PMID:The pneumotoxicant paraquat induces IL-8 mRNA in human mononuclear cells and pulmonary epithelial cells. 814 10

Pulmonary fibrosis is a frequent and serious complication of scleroderma whose pathophysiology remains poorly understood. The alveolar structures are infiltrated by activated chronic inflammatory cells, alveolar macrophages and polymorphonuclear neutrophils in particular and these could play a determining role. We have studied the state of activation of alveolar macrophages and monocytes circulating in these patients who presented with scleroderma and interstitial pulmonary involvement and also in healthy subjects. The neutrophil alveolitis observed in the patients is accompanied by a raised level of interleukin-8 secretion by the alveolar macrophages compared to the healthy subjects. Interleukin-8 is an important chemotactic molecule for polymorphonuclear neutrophils in the lung. The neutrophil alveolitis is accompanied by a breakdown in the equilibrium of elastase-antielastase which could participate in the development of alveolar lesions leading to fibrosis. In addition to the activation of macrophages, there is an activation of monocytes marked by the increase in secretion of interleukin-6 and interleukin-8 in vitro during the progression of the disease of scleroderma. Thus, alveolar inflammation is integrated with the overall systemic inflammation whose causes remain unknown.
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PMID:[Scleroderma and alveolar inflammation]. 865 Apr 11

Although the pathological patterns of interstitial pneumonia associated with collagen vascular disease (CVD-IP) resemble those of usual interstitial pneumonia in idiopathic interstitial pneumonia (IIP), the clinical features of CVD-IP and IIIP are quite different. We evaluated the differences between these conditions, with regard to the expression of genes in cells obtained by bronchoalveolar lavage. The reverse transcription-polymerase chain reaction was used to measure the levels of mRNA for IL-1 beta, TNF-alpha, IL-8, TGF-beta, PDGF-B, and IGF-1, and no significant differences were found between patients with CVD-IP and those with IIP. However, differential display analysis revealed a fragment that can be considered to have been derived from an unknown gene mRNA, and this was found only in patients with pulmonary fibrosis associated with progressive systemic sclerosis. Expression of specific genes may differentiate CVD-IP from IIP.
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PMID:[Pulmonary manifestation of collagen vascular diseases: role of cytokines in interstitial pneumonia associated with collagen vascular diseases]. 875 19

Chronic lung disease (CLD) of prematurity is associated with an initial increase in pulmonary neutrophils followed by pulmonary fibrosis. We determined whether the proinflammatory cytokines, IL-1 beta and IL-6, were increased in the bronchoalveolar lavage fluid obtained from nine infants (median gestation 25 wk, birthweight 820 g) who developed CLD, seven (28 wk, 1110 g) who recovered from the respiratory distress syndrome (RDS), and four (38 wk, 2690 g) control infants. IL-1 beta and IL-6 protein were both increased in the bronchoalveolar lavage fluid from the CLD groups when compared with the RDS and control groups. This difference for both the cytokines was most marked on d 10 of age, when results from infants with and without CLD were compared (IL-1 beta, 4.6 versus 1.1 ng/mL, p < 0.05; and IL-6, 9.5 versus 1.5 ng/mL, p < 0.05). Immunocytochemistry of lavage cells for IL-1 beta, IL-6, and IL-8 protein showed alveolar macrophages to contain all three cytokines, with lesser staining evident in neutrophils, and in epithelial cells occasionally obtained by lavage. The contribution of alveolar macrophages and luminal cells to the increase in IL-6 and IL-1 was determined by performing semiquantitative reverse transcription-polymerase chain reactions on RNA extracted from lavage cells. IL-6 mRNA expression was increased in lavage cells from the CLD infants when compared with the RDS group. However, the expression for IL-1 beta and IL-8 mRNA was similar in both groups. These results suggest that IL-1 beta, IL-6, and IL-8 may contribute to the pathogenesis of CLD, and that, in CLD, IL-6 may be produced by cells within the air spaces.
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PMID:Increase in interleukin (IL)-1 beta and IL-6 in bronchoalveolar lavage fluid obtained from infants with chronic lung disease of prematurity. 882 73

Drug can cause various types of lung damages, with drug-induced pneumonitis (including acute interstitial pneumonia, usual interstitial pneumonia, desquamative interstitial pneumonia, nonspecific interstitial pneumonia, bronchiolitis obliterans with organizing pneumonia, eosinophilic pneumonia and hypersensitivity pneumonitis) being the most important among them. The incidence and the causative agents of drug induced pneumonitis have varied over time. Before 1980, anticancer agents and gold salts were the main drugs, and the number of causative drugs (61) and case reports was small. Recently, pneumonitis has increasingly been caused by Chinese herbal medicines, antibiotics, chemotherapy agents, anti-inflammatory drugs, analgesics, cytokines, and gold salts, and the number of case reports and drugs involved (177) has increased. Drug-induced pneumonitis has characteristics that depend on the causative agent. Review of our patients and reports in Japan revealed the following. Pneumonitis caused by anti-inflammatory drugs, analgesics, and antibiotics generally develops at 1-2 weeks after starting administration, and bronchoalveolar lavage and histologic examination of lung biopsies reveals the features of eosinophilic pneumonia. Such pneumonitis is associated with a high frequency of a positive drug lymphocyte stimulation test (DLST), and has a good outcome. Conversely, with pneumonitis caused by anticancer and immunosuppressive agents, the onset is often delayed and the disease has features of diffuse interstitial pneumonia and pulmonary fibrosis. The frequency of a positive DLST is low, and the outcome is generally poor. Pneumonitis induced by Chinese herbal medicines, gold salts, and antituberculosis agents has intermediate features between the above two types :i.e., it develops after 2-3 months or six months (gold salts), and resembles either eosinophilic pneumonia, BOOP or interstitial pneumonia. For in vitro identification of causative drugs, the DLST and the leukocyte migration inhibition test (LMIT) are generally used. The latter test is superior in sensitivity, suggesting that the mechanism of this test involves cytokines such as IL-1 alpha, IL-1 beta, IL-2, TNF-alpha, and IL-8.
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PMID:[Drug-induced pneumonitis]. 1006 54

Epithelial cell injury is the common manifestation of lung injury. Contributing to such injury of epithelial cells is apoptosis. Although apoptosis is part of the normal process of epithelial renewal, in excess it is pathologic. We previously demonstrated the excessive apoptosis of lung epithelial cells and the upregulation of Fas and Fas ligand (FasL) in fibrosing lung diseases. We also showed that inhalation of anti-Fas antibody induced lung injury and fibrosis in mice. Interleukin (IL)-8 is one of the most important cytokines in the pathophysiology of acute lung injury and pulmonary fibrosis. In this study we investigated whether Fas ligation induces IL-8 secretion in addition to apoptosis in bronchiolar epithelial cells in vitro. Bronchiolar epithelial cells underwent apoptosis and also secreted IL-8 in response to tumor necrosis factor (TNF)-alpha or Fas ligation. New gene expression and protein synthesis were not necessary for Fas ligation- and TNF-alpha- mediated apoptosis, but were necessary for IL-8 secretion. We further found that Fas ligation induced activation of nuclear factor-kappa B. We conclude that the Fas/FasL pathway not only mediates apoptosis but also plays a proinflammatory role, and that stimulation of the Fas/FasL pathway in bronchiolar epithelial cells leads to IL-8 production, which may amplify the inflammatory cascade in lung injury and pulmonary fibrosis.
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PMID:Induction of interleukin-8 secretion and apoptosis in bronchiolar epithelial cells by Fas ligation. 1046 Jul 62

In bronchial asthma, eosinophils and neutrophils are activated, so that the production of active oxygen species increases, causing airway epithelial injury. Suplatast tosilate (IPD Capsules) is a novel immunomodulating antiallergic drug that acts against bronchial asthma through a new mechanism. To evaluate the effects of suplatast tosilate on mononuclear cell-mediated IL-8 production, and neutrophil-mediated active oxygen species production at sites of inflammation, we collected peripheral blood from healthy subjects and separated the neutrophils as well as mononuclear cells. Suplatast tosilate was added at a concentration of 1 x 10(-6), 1 x 10(-7) or 1 x 10(-8) M, and cells were incubated for 10 min at 37 degrees C. Then, the neutrophils were stimulated with fMLP, and luminol-dependent chemiluminescence (LDCL) was measured, while IL-8 production was determined with an ELISA kit. Suplatast tosilate (1 x 10(-6) M) inhibited neutrophil-mediated active oxygen species production by 12.4% in terms of the peak, and by 16% in terms of the integral value. Moreover, it significantly inhibited mononuclear cell-mediated IL-8 production at concentrations of 1 x 10(-6), 1 x 10(-7) and 1 x 10(-8) M, in a concentration-dependent manner. This study indicated that suplatast tosilate may inhibit neutrophil infiltration by suppressing monocyte-mediated IL-8 production, and it may also inhibit the activation of neutrophils at sites of inflammation. These results suggest the possibility that suplatast tosilate may not only be of benefit for asthma, but may also prevent or control pulmonary fibrosis or emphysema, for which no effective treatment is presently available.
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PMID:Effects of suplatast tosilate (IPD Capsules) on the production of active oxygen by neutrophils and of IL-8 by mononuclear cells. 1140 12

The aim of the present investigation was to evaluate lung function and the time course of serum concentration of selected cytokines known to be involved in pulmonary fibrosis, in 39 patients with stages IIB, III and IV Hodgkin's disease submitted to intermediate-high dose chemotherapy, (epirubicin, vincristine, cyclophosphamide, etoposide, prednisone) followed by radiotherapy. Lung function tests were performed before, at the end of treatment and after a follow-up of more than 12 months from the end of the combined therapy. Tumor necrosis factor alpha, fibronectin and Interleukins 4, 6 and 8 were determined on serum samples collected at the same time intervals. In the patients, spirometric parameters apparently improved whereas diffusing capacity for CO (DLCO) decreased, TNF-alpha concentrations constantly decreased, fibronectin and IL-8 showed a tendency to increase, but Interleukins 4 and 6 did not show significant modifications. No significant correlations were observed between the changes of lung function tests and serum cytokine concentrations, probably because cytokine serum levels were not able to reflect events occurring in the alveolar phase.
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PMID:Lung function and serum concentrations of different cytokines in patients submitted to radiotherapy and intermediate/high dose chemotherapy for Hodgkin's disease. 1217 34


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