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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 resulting from diverse etiologies is characterized by proliferation of fibroblasts and excessive accumulation of interstitial collagen. Whether fibrosis is associated with selective expansion of fibroblast subpopulations differing in amounts or types of collagens synthesized is unknown. We have previously isolated lines and clones of normal murine lung fibroblasts based on the presence of the Thy 1 surface antigen. These subpopulations differ in morphology, growth characteristics, and display of class II major histocompatibility complex antigens (R.P. Phipps, D.P. Penney, P. Keng, H. Quill, A. Paxhia, S. Derdak, and M. E. Felch. Am. J. Respir. Cell Mol. Biol. 1: 65-74, 1989). We evaluated the amounts and types of collagen and fibronectin synthesized by Thy 1+ (Fib2-T-3+) and Thy 1- (Fib2-T-4-) lung fibroblast lines and clones. Thy 1+ fibroblast line synthesized two- to threefold more collagen and noncollagen protein than the Thy 1- line. In contrast, both the Thy 1+ and Thy 1- lines synthesized similar amounts of fibronectin. Thy 1+ and Thy 1- lines and clones expressed mRNA for alpha 1(I)-and alpha 1(III)-procollagen and synthesized both types (predominantly type I and lesser amounts of type III) of collagen, protein, and mRNA. The fibroblast clones varied significantly in total collagen and fibronectin production, with one Thy 1- clone (D3) synthesizing the largest amount of collagen but relatively little fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential collagen and fibronectin production by Thy 1+ and Thy 1- lung fibroblast subpopulations. 135 33

The occurrence of autoantibodies in patients with systemic sclerosis has suggested a role for immune dysregulation in this disease. Recent genetic studies have concentrated on the major histocompatibility complex-encoded antigens and found an association of particular HLA-DQ alleles with anticentromere antibodies. Although the role of major histocompatibility complex antigens and autoantibodies in the pathogenesis of systemic sclerosis remains unclear, determination of major histocompatibility complex alleles may have clinical value in identifying patients who are at increased risk for development of pulmonary fibrosis or rapidly advancing skin disease. A variety of environmental factors have been associated with systemic sclerosis-like skin diseases, including silica, vinyl chloride, paraffin, adulterated L-tryptophan, and "toxic" rapeseed oil. It has been suggested that silicone used during breast augmentation may be a risk factor for development of systemic sclerosis, but ascertainment bias in case reporting makes interpretation of these studies difficult. The heterogeneity of clinical features, major histocompatibility complex status, and autoantibody profiles in systemic sclerosis suggest that this disorder may actually be a group of distinct disorders, each of which has its own characteristic genetic and environmental predisposing risk factors.
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PMID:Genetic and environmental factors in systemic sclerosis. 145 81

The expression of class II molecules (Ia) of the major histocompatibility complex by isolated alveolar macrophages (AM) and alveolar type II cells from the lungs of rats with bleomycin-induced pulmonary fibrosis was examined. The percentage of Ia-positive AM and type II cells from rats treated with bleomycin as detected by flow cytometry was increased three times and two times, respectively, over the values obtained from control rats. The relative density of Ia expression, determined with a radioimmunoassay technique, showed a 50% increase in Ia density on AM and a 35% increase on type II cells. Recombinant interferon-gamma increased the expression of Ia on type II cells in vitro by 35% to the level obtained on type II cells in bleomycin-induced lung disease. We conclude that the increase of Ia expression on cells of the immune system and on pulmonary epithelial cells may have an important role in the initiation and/or amplification of inflammatory reactions in the lung and may contribute to the development of pulmonary fibrosis.
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PMID:Class II antigens of the major histocompatibility complex are increased in lungs of bleomycin-treated rats. 170 54

The purpose of this investigation was to determine whether subpopulations of murine lung fibroblasts produced interleukin 1 (IL 1). We previously identified two major populations of pulmonary fibroblasts based on the presence or absence of Thy-1. Thy-1+ and Thy-1- subsets synthesize fibronectin and type I and III collagen, but only the Thy-1- population displays class II major histocompatibility complex antigens after stimulation with interferon-gamma and presents antigen to T helper clones. Interestingly, in the current study we determined that only Thy-1- fibroblast lines and clones synthesized IL 1. Although constitutive production was low, tumor necrosis factor -alpha (TNF-alpha) stimulated 5-20-fold increases in IL 1 production in Thy-1- fibroblasts. The Thy-1+ fibroblasts did not produce IL 1 even after TNF-alpha treatment. Northern blot analysis of TNF-alpha treated cells revealed that in the Thy-1- subset increased mRNA levels for IL 1 alpha were detected, while IL 1 beta mRNA was not detected. Furthermore, IL 1 activity from TNF-alpha-treated Thy-1- fibroblast membranes and supernatants was completely neutralized by IL 1 alpha-specific antibodies. These observations support the hypothesis that the antigen-presenting Thy-1- subset is important for promoting the inflammation associated with pulmonary fibrosis. In addition, the existence of functional subsets of lung fibroblasts is further substantiated by differential expression of IL 1.
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PMID:Differential expression of interleukin 1 alpha by Thy-1+ and Thy-1- lung fibroblast subpopulations: enhancement of interleukin 1 alpha production by tumor necrosis factor-alpha. 197 21

From evidence of interpatient variability in normal tissue sensitivity to radiotherapy and from radiation studies using inbred mouse strains, it is hypothesized that individual variation in susceptibility to radiation-induced pulmonary fibrosis is genetically controlled. A genetic model has been developed from the fibrosis-prone C57BL/6J and the fibrosis-resistant C3Hf/Kam mouse strains. Inheritance of the fibrotic phenotype was characterized in F1 and F2 (F1 intercross) generations derived from the parental strains. Genetic mapping was used to determine whether the quantitative trait loci (QTL), which influence susceptibility to bleomycin-induced lung fibrosis in these progenitor strains, could be implicated in susceptibility to radiation-induced lung fibrosis. Mice were treated with 14 or 16 Gy (60Co) to the whole thorax. The doses were selected to investigate the response at the LD50 and LD100 of C3Hf/Kam mice. The animals were sacrificed 33 weeks after treatment or when moribund. The percentage of lung with fibrosis for each mouse was quantified with image analysis of a histological section of the lung. For both the 14- and 16-Gy data sets, heritability was estimated at 38 +/- 11%, and the number of genetic factors influencing susceptibility to pulmonary fibrosis was estimated to be one or two. Two hundred fifty-five F2 intercross mice were genotyped with markers at the bleomycin loci on chromosomes 11 and 17 (chromosome 17 marker is at the major histocompatibility complex). Genetic linkage was established for the marker on chromosome 17 (P = 3.0 x 10(-6)), which accounts for 6.6% of the F2 phenotypic variance but not for the markers surrounding the QTL on chromosome 11 (P = 0.37). The inheritance data suggested that susceptibility to radiation-induced pulmonary fibrosis is a heritable trait controlled by two genetic loci, and through genomic mapping, a QTL on chromosome 17 was identified as one of the loci.
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PMID:Murine susceptibility to radiation-induced pulmonary fibrosis is influenced by a genetic factor implicated in susceptibility to bleomycin-induced pulmonary fibrosis. 939 51

In some patients, chemotherapy (CHT) of cancer can result in pulmonary inflammation and fibrosis, eventually leading to respiratory insufficiency. As animal studies have underlined the importance of major histocompatibility complex (MHC) genes in the susceptibility to bleomycin (BLM)-induced pulmonary fibrosis, the authors typed human leukocyte antigen-DR (HLA-DR) and tumor necrosis factor (TNF) genes in patients treated for Hodgkin's disease by a therapy including bleomycin. Patients were divided into pulmonary responders (PR) (n=21) or nonresponders (PNR) (n=20) on the basis of pulmonary alterations detected on chest radiography and the cumulated amount of BLM injected. The incidence of TNFa2, a microsatellite allele in the promoter region of the TNFB gene reported to be associated with increased TNF-a production, was significantly higher in PR than PNR (65% versus 19%). HLA-DRB1*15 showed a weak but nonsignificant association with the PR phenotype (50% versus 14%), as well as HLA-DRB1*03 (30% versus 19%) and TNFA-308*2 (30% versus 14%). TNFa2 and DR15 were independent risk factors and the occurrence of either genetic marker was 85% versus 29% in the PR and PNR groups respectively. Thus, the polymorphic TNFa2 microsatellite is associated with a risk of chemotherapy-induced pulmonary fibrosis.
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PMID:Risk of chemotherapy-induced pulmonary fibrosis is associated with polymorphic tumour necrosis factor-a2 gene. 1203 Jul 33

Susceptibility to pulmonary fibrosis following environmental insults or cytotoxic cancer therapies has a genetic component. In mouse strains differing in susceptibility to bleomycin-induced lung fibrosis, we show highly significant linkage to only two loci. The first locus on chromosome 17 in the major histocompatibility complex (MHC), LOD = 17.4, named Blmpf1, is highly significant in both males and females, and accounts for approximately 20% of the phenotypic variance. We confirmed the presence of Blmpf1 in MHC congenic mice and narrowed the region to 2.7 cM in a reduced MHC congenic strain. The second locus on chromosome 11, LOD = 5.6, named Blmpf2, is significant in males only. A model including an interaction between Blmpf1 and Blmpf2 best fit the data in males. We confirmed Blmpf2 in a chromosome substitution strain, C57BL/6J-11(C3H), and found that its presence reduces the severity of fibrosis. Functional studies of bleomycin hydrolase activity indicate that this enzyme modulates bleomycin-induced pulmonary fibrosis, suggesting that it may be a candidate gene for Blmpf2. The data suggest sex-specific models of susceptibility to bleomycin-induced lung fibrosis, with an interaction between Blmpf2 and Blmpf1 for the more susceptible males and Blmpf1 as the major locus in females. A putative mechanism for the interaction between the two loci in males is that bleomycin hydrolase functions as an MHC class I epitope-processing protease.
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PMID:Bleomycin hydrolase and a genetic locus within the MHC affect risk for pulmonary fibrosis in mice. 1214 Jan 88

Improvements in biological research and the development of new techniques for human health protection require animal experimentation of various species. In particular, animal models are always necessary to test new therapies for the treatment of various human diseases. The latest advances in molecular biology involving genetic modification are aimed at developing new animal models of human diseases that are not present in spontaneous murine broods or obtainable with other experimental manipulations. Transgenic techniques and, in particular, the possibility to directly modify specific genetic information in the experimental animal have led to the acquisition of important knowledge on the physiologic functions of many proteins and their function in the course of various diseases. The advent of new transgenic animals is opening up new and interesting frontiers, full of hope and opportunity, for the research into pulmonary diseases. New advances in cystic fibrosis, emphysema, and pulmonary fibrosis have been made through the study of a large number of proteins implicated in the complex of acute and chronic inflammatory processes of lung parenchyma, which are responsible for permanent changes in organ structure and function. Recent studies carried out on murine inbred strains have yielded significant new data on the multifactor origin of pulmonary disease, because of their correlation with the major histocompatibility complex (H2 in mice) or through the different genetic map of the strains. Today it is possible to outweigh or potentiate the function and expression of some genes, obtaining a deficit or abundance, respectively, of specific proteins. These techniques have permitted and will continue to permit the development of new models of human disease, leading to further therapeutic advances as a consequence.
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PMID:Genetically modified animals as models of pulmonary disease. 1261 82

Most studies have suggested that ethnic factors impact significantly on systemic sclerosis. Extensive epidemiologic studies have been carried out in white individuals, and limited data suggest that blacks are affected twice as frequently; Japanese patients have a lower prevalence than whites. This highest rate that has been described has been in Choctaw Native Americans. Blacks have a lower age at onset, as well as a higher frequency of diffuse skin involvement, pulmonary disease, and an overall worse prognosis than whites. Limited data in Hispanics and Native Americans suggest that they have more severe disease than whites. Whites have the highest frequency of anti-centromere antibodies (associated with limited skin involvement and less pulmonary fibrosis), whereas blacks have a higher frequency of anti-ribonucleoprotein and fibrillarin autoantibodies; the latter is a nucleolar antibody associated with a poorer prognosis. Ethnic differences are also seen for associations with non-major histocompatibility complex genes, such as FBN1 (fibrillin) genes, in Choctaws and Japanese and SPARC (osteonectin) in whites, Hispanics, and Choctaws. Although these facts do not entirely rule out socioeconomic factors associated with ethnicity, nevertheless ethnicity has an important impact on the pathogenesis of systemic sclerosis, perhaps because of genetic factors.
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PMID:Ethnicity and race and systemic sclerosis: how it affects susceptibility, severity, antibody genetics, and clinical manifestations. 1262 48

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown etiology, with an appearance of usual interstitial pneumonia on lung biopsy. To-date, about a 100 families diagnosed with IPF have been described. Familial IPF is defined as histologically confirmed IPF occurring in two or more members of a family. Familial pulmonary fibrosis is hereditary, most probably as a feature which is autosomal dominant with variable penetration. Since 2002, we have been following two families with IPF, referred to in the present article as A and B. The patients in Family A included brother, sister, and sister's daughter. We examined two closest relatives of the patients in family A who are healthy. The patients in Family B included father and his two children. In Family B, we examined six other closest relatives, all of whom proved healthy. In all cases, IPF diagnosis was confirmed histologically. We examined human leukocyte antigen (HLA) alleles in both families, including antigens Class I (locus A, B, and C) and Class II (locus DR). On the basis of the results obtained it is impossible to determine the relation between major histocompatibility complex (MHC) polymorphisms and the incidence of the disease.
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PMID:Familial idiopathic pulmonary fibrosis. 2383 99


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