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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major role of TNF in pulmonary fibrosis is supported by the following evidences obtained from pulmonary fibrosis induced in mice by bleomycin or silica particles; 1) these diseases are associated with a marked and lasting increase of the TNF mRNA within the lung, 2) they can be prevented by a treatment with anti TNF antibody or aggravated by a perfusion of mouse recombinant TNF, 3) an infusion of TNF-alpha can reproduce the alterations observed during pulmonary fibrosis such as growth of fibroblasts, collagen deposition, cell necrosis.
Eur Cytokine Netw
PMID:Is "tumor necrosis factor" the major effector of pulmonary fibrosis? 171 90

IL-1 is a key cytokine that promotes pulmonary inflammation and fibrosis, as a result of its ability to stimulate lung fibroblast proliferation and collagen synthesis, two hallmarks of fibrosis. The IL-1 receptor antagonist (IL-1Ra) is an important natural inhibitor of IL-1-mediated functions. In models of pulmonary fibrosis induced by chemotherapeutic agents or noxious particles, administration of IL-1Ra significantly ameliorates lung fibrosis. Lung tissue undergoing an inflammatory response shows elevations in IL-1Ra, although it is not clear which pulmonary cells are responsible for the IL-1Ra synthesis. The purpose of this research was to determine whether Thy-1+ and Thy-1- subsets of mouse lung fibroblasts were capable of synthesizing IL-1Ra. In this report, it is demonstrated for the first time that lung fibroblasts are capable of synthesizing IL-1Ra. Both Thy-1+ and Thy-1- parental lines and clones constitutively express IL-1Ra mRNA. Quantitation of IL-1Ra protein indicates that Thy-1+ and Thy-1- fibroblasts secrete similar levels of secreted but not intracellular IL-1Ra. Thy-1- fibroblasts accumulate higher levels of IL-1Ra intracellularly. Moreover, fibroblast-conditioned supernatants containing IL-1Ra significantly suppress the mitogenic response of a T cell clone, D10G4.1, to concanavalin A and IL-1 beta. Overall, our observations indicate that Thy-1+ and Thy-1- fibroblasts release IL-1Ra and possess an IL-1-specific inhibitory activity in their supernatants. In vivo, fibroblast-derived IL-1Ra may serve to regulate IL-1-mediated effects in an autocrine and/or paracrine fashion to maintain homeostasis in the pulmonary interstitium.
J Interferon Cytokine Res 1995 Jan
PMID:Synthesis of interleukin-1 receptor antagonist by Thy-1+ and Thy-1- murine lung fibroblast subsets. 764 35

We explored the role of interleukin 1 (IL-1) in two models of pulmonary fibrosis (PF), elicited in mice by the intra-tracheal instillation of bleomycin or silica. In both models, administration of IL-1 receptor antagonist (IL-1ra) by an osmotic minipump implanted i.p., at a rate of 0.5 microgram/h, completely prevented the collagen deposition, as evaluated by the lung hydroxyproline content on day 15 after instillation. IL-1ra had little or no influence on the number of cells recovered from the broncho-alveolar lavage. Study of histological sections suggests that IL-1ra globally decreased the proportion of damaged lung and particularly in silica the formation of nodules with a rich content in collagen fibrils. IL-1ra was also effective in reducing the lung hydroxyproline content when given on day 25 after instillation of bleomycin or silica, indicating that it may reverse established PF. This study indicates that IL-1ra might be useful for the treatment of incipient or established pulmonary fibrosis.
Cytokine 1993 Jan
PMID:Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica. 768 5

Recombinant rat gamma-interferon was found to inhibit collagen accumulation induced by the intratracheal administration of bleomycin in rat lungs. gamma-Interferon also elicited a reduction in histamine content in the lungs of the bleomycin-treated rats; however, this agent did not cause any obvious changes in inflammatory cell infiltration into the lung. These results suggest that gamma-interferon inhibits the development of pulmonary fibrosis by suppressing collagen synthesis and could thus be used as a therapeutic agent for preventing this condition.
Lymphokine Cytokine Res 1993 Apr
PMID:Effects of gamma-interferon on collagen and histamine content in bleomycin-induced lung fibrosis in rats. 768 80

Transforming growth factor-beta (TGF-beta) and interleukin-1 (IL-1) are essential participants in the development of pulmonary fibrosis. Administration of inhibitors to either cytokine can prevent the onset and progression of lung fibrosis in animal models. In this report, stable Thy-1+ and Thy-1- murine lung fibroblast subpopulations were analyzed for expression of the three mammalian TGF-beta isoforms. TGF-beta 1, TGF-beta 2, and TGF-beta 3 mRNA transcripts were detected by reverse transcriptase-PCR in both murine fibroblast subsets. Most of the TGF-beta produced by fibroblasts is latent; however, a small amount of active TGF-beta can be detected using a sensitive mink lung cell bioassay. By incorporating neutralizing anti-TGF-beta isoform-specific antibodies, it was determined that TGF-beta 1 is the predominant isoform present in both the active and the latent forms. Overall, Thy-1- fibroblasts secrete twice as much latent TGF-beta as the Thy-1+ subset. To investigate whether a link exists between TGF-beta and IL-1, the effect of TGF-beta 1 on the expression of IL-1 receptor type I (IL-1RtI) by fibroblast subsets was assessed by flow cytometry and Scatchard analysis. TGF-beta 1 significantly down-regulates the expression of IL-1RtI by Thy-1+ fibroblasts, but not by Thy-1- fibroblasts. A functional consequence of this down-regulation of the IL-1RtI is that it makes Thy-1+ fibroblasts less responsive to IL-1-mediated induction of IL-6 protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphokine Cytokine Res 1994 Oct
PMID:Expression of TGF-beta isoforms by Thy-1+ and Thy-1- pulmonary fibroblast subsets: evidence for TGF-beta as a regulator of IL-1-dependent stimulation of IL-6. 785 60

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.
Cytokine 1993 Sep
PMID:The pneumotoxicant paraquat induces IL-8 mRNA in human mononuclear cells and pulmonary epithelial cells. 814 10

Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF beta), a fibrogenic and radiation-inducible cytokine, was studied from 1-16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF beta protein in bronchoalveolar lavage (BAL) fluid peaking at 3-6 weeks as compared to sham-irradiated control rats. Steady state TGF beta mRNA expression as shown by whole lung northern blot assay paralleled the TGF beta protein expression in BAL fluid. The peak of TGF beta protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8-10 weeks after irradiation. In conclusion. TGF beta and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.
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PMID:Radiation-induced lung injury in vivo: expression of transforming growth factor-beta precedes fibrosis. 887 98

Bleomycin (BLM) induction of lung fibrosis in mice is an established model to study the mechanism of pulmonary fibrosis. Cytokine secretion has been implicated as a fundamental component of the lung fibrotic process observed in response to BLM. Among the cytokines implicated in lung fibrosis, Tumor necrosis factor (TNF) alpha has been considered to play a fundamental role. In the present study, we characterized the cellular sources of TNF during BLM-induced lung injury and examined the importance of TNF receptors in this process. To characterize the expression of TNF, we utilized two strains of mice, one sensitive (C57BL/6) and one resistant (BALB/c) to BLM-induced lung injury. Mice received BLM (120 mg/kg total) or saline, as control, by multiple subcutaneous injections. BLM induced the development of inflammation in subpleural areas only in the lungs of BLM-sensitive mice. These subpleural areas were characterized by infiltration of CD68-positive macrophages and increased collagen deposition. BLM enhanced the expression of TNF mRNA in BLM-sensitive, but not in BLM-resistant, mice. In situ hybridization studies localized the expression of TNF in the areas of BLM-induced inflammation in 6% and 27% of macrophages at 14 and 21 days post BLM treatment. In addition to TNF, BLM exposure resulted in the upregulated expression of transforming growth factor (TGF)-beta 1, but not interleukin (IL)-1, mRNA in the lungs of both murine strains at 14 and 21 days. This upregulated expression of TGF-beta 1 mRNA was greater in the lungs of BLM-sensitive mice. In separate experiments, double TNF receptor knockout mice were exposed to BLM. These animals demonstrated an increased expression of TNF, but not TGF-beta 1, mRNA in response to BLM and did not exhibit histologic evidence of lung injury following BLM exposure. In summary, the upregulation of TNF mRNA in macrophages correlated with the appearance of inflammation following BLM exposure and was limited to the BLM-sensitive strain. Furthermore, in addition to the release of the TNF ligand, it appears that the presence of TNF receptors is necessary for the development of BLM-induced lung injury, and signaling through these receptors may contribute to the regulation of the TGF-beta 1 mRNA expression observed in response to bleomycin. These results provide further support for a role of macrophages and TNF in the induction of lung inflammation.
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PMID:Expression of TNF and the necessity of TNF receptors in bleomycin-induced lung injury in mice. 983 61

Monocyte chemoattractant protein-1 (MCP-1) is a member of chemokines with chemoattractant activity for monocytes, T cells, mast cells, and basophils. Precursor mRNA or protein was detected at high levels in the lesions of several diseases, such as pulmonary fibrosis, rheumatoid arthritis, atherosclerosis, and some types of tumors. The regulation of MCP-1 production and the role of this chemokine in pathophysiologic states, however, remain largely unknown. In this study, using an enzyme-linked immunosorbent assay (ELISA), we measured the circulating MCP-1 levels in 405 healthy Japanese subjects of various ages, eliciting a profound age-dependent MCP-1 increase. Multivariate regression analysis revealed that significant predictors of MCP-1 value for males were age (p = 0.033) and serum triglyceride (p = 0.039). For females, age was also a significant predictor (p = 0.00002). One possible explanation is that the plasma MCP-1 concentration might reflect the existence of atherosclerosis, although the plasma MCP-1 concentration from patients with coronary artery disease or cerebrovascular accidents appears not to differ from age-matched, disease-free controls. This is the first report linking an increase in a particular chemokine level with aging.
J Interferon Cytokine Res 1999 Oct
PMID:Increase in circulating levels of monocyte chemoattractant protein-1 with aging. 1054 58

Interleukin-4 (IL-4) is known to activate mononuclear cells as well as fibroblasts, all of which are important in the pathogenesis of pulmonary fibrosis. To investigate the potential role of this cytokine, lung IL-4 expression was examined in a murine model of bleomycin-induced pulmonary fibrosis. Lung fibrosis was induced in CBA/J mice by endotracheal injection of bleomycin on day 0. On selected days after treatment, lungs were harvested for reverse transcriptase polymerase chain reaction (RT-PCR), Northern, in-situ hybridization and immunohistochemical analyses. RT-PCR and Northern analyses revealed significant increases in lung IL-4 mRNA content between days 3 and 14 after induction of lung injury, which decreased toward control level after day 21. Both in-situ hybridization and immunohistochemistry showed low or undetectable IL-4 expression in control lungs and in injured lungs before day 3 after bleomycin injection. There was however elevated expression in mononuclear cells and macrophages between days 3 and 14, localized to areas of active fibrosis. These results demonstrate that IL-4 is upregulated significantly in this model. They suggest a potential role for this cytokine in pulmonary fibrosis, perhaps via its ability to stimulate and amplify the inflammatory response, stimulate collagen synthesis in fibroblasts, and thus promote the progression to fibrosis and end stage lung disease.
Cytokine 2001 Aug 07
PMID:Lung interleukin-4 gene expression in a murine model of bleomycin-induced pulmonary fibrosis. 1155 83


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