Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Causal links have been documented between silica and rheumatoid arthritis, lupus erythematosus, systemic sclerosis and glomerulonephritis. Two different effects of silica have been suggested, an enhanced inflammatory response in the pulmonary region (e.g. activation of alveolar macrophages) and dysregulation of autoimmunity. Based on our previous reports showing in vitro activation of peripheral T cells by silica and reduced regulatory function of the peripheral CD4(+)CD25(+) fraction in which FoxP(3)+ regulatory T cells (Treg) are located, reconstitution of the CD4(+)CD25(+) fraction in silicosis patients (SILs) was investigated. Since T cells in peripheral CD4(+)CD25(+) and CD4(+)CD25(-) (effector T cells; Teff) fractions from SILs showed higher expression of pd-1 (a marker gene for T cell activation) in comparison to that of healthy donors (HDs), chronic T cell activation was considered to have occurred in SILs. In this study, a higher expression of the CD95/Fas molecule in Treg was recorded from silicosis patients (SILs) compared to healthy donors (HDs), and excess loss of FoxP3(+) Treg in freshly isolated peripheral blood mononuclear cells (PBMCs) from SILs relative to HDs was demonstrated when these cells were cultured with silica ex vivo, whereas CD25(+) cells were not reduced due to contamination of activated Teff in the CD4(+)CD25(+) fraction. The activation of both Teff and Treg results in reconstitution of the peripheral CD4(+)CD25(+) fraction, loss of Treg and contamination of activated Teff, resulting in reduction of the number and function of Treg. These results contribute to our understanding of the development of autoimmune diseases found in SILs.
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PMID:Reductive alteration of the regulatory function of the CD4(+)CD25(+) T cell fraction in silicosis patients. 2124 59

Silicosis patients suffer from pulmonary fibrosis caused by silica inhalation, as well as autoimmune diseases known as the adjuvant effects of silica. Caplan syndrome complicated with rheumatoid arthritis (RA) is well known epidemiologically, and the incidence of complicated systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and antineutrophilic cytoplasmic antibody (ANCA)-related nephritis have been reported frequently in silicosis patients. To explore the detailed mechanisms of silica-induced dysregulation of autoimmunity, we had focused on Fas/CD95 and Fas-mediated apoptosis because Fas is one of the most important molecules regarding apoptosis of lymphocytes and its alteration makes some T cells survive longer. Additionally, if the long-survived T cells include the self-recognizing T-cell clones, it is easily thought that autoimmune diseases will appear in this situation. Furthermore, regulatory T cells (Treg) showing CD4+25+ and forkhead box P3 (FoxP3)-positive have been a central player in regulating activation of self- and foreign-antigen recognizing T cells, and it has been reported that activation of Treg causes its higher expression of Fas/CD95. Thus, in this review, we introduce the alteration of Fas and related molecules as found in silicosis and also present the Treg function of the CD4+25+ fraction in peripheral blood mononuclear cells derived from silicosis patients.
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PMID:Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apoptosis in T lymphocytes derived from silicosis patients. 2132 60

Autoimmune disorders are induced by various environmental and occupational substances. Among the most typical factors involving these substances, it is well known that silica exposure causes not only pulmonary fibrosis known as silicosis, but also induces autoimmune diseases such as rheumatoid arthritis known as Caplan's syndrome, systemic sclerosis, systemic lupus erythematosus, and anti-neutrophil cytoplasmic autoantibody (ANCA)-related vasculitis/nephritis. To investigate the immunological effects of silica, a focus on the occurrence of autoimmune dysfunction may clarify these autoimmune diseases and develop effective tools for observing silicosis patients (SIL). In this review, our investigation concerns the autoantibodies found in SIL, alteration of CD95/Fas and related molecules in SIL, case-oriented and in vitro analyses of silica-induced activation of responder and regulatory T cells, and supposed mechanisms of reduction of CD4+25+FoxP3+ regulatory T cells (T(reg)) in SIL. Further studies are required to investigate Th17 and the interaction with T(reg) in SIL to understand the cellular and molecular mechanisms of environmental and occupational autoimmune disorders.
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PMID:Environmental factors producing autoimmune dysregulation--chronic activation of T cells caused by silica exposure. 2222 3

Silica particles and asbestos fibers, which are known as typical causatives of pneumoconiosis, induce lung fibrosis. Moreover, silicosis patients often complicate with autoimmune diseases, and asbestos-exposed patients suffer from malignant diseases such as pleural mesothelioma and lung cancer. We have been conducting experimental studies to investigate altered regulation of self-tolerance caused by silica exposure, including analyses using specimens such as plasma and immunocompetent cells obtained from silicosis patients, as a means of examining the supposition that silica exposure induces molecular and cellular biological alterations of immune cells. These approaches have resulted in the detection of several specific autoantibodies, alterations of CD95/Fas and its related molecules, and evidence of chronic activation of responder T cells and regulatory T cells following silica exposure. In this review, we present details of our investigations as an introduction to scientific approaches examining the immunological effects of environmental and occupational substances.
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PMID:Silica exposure and altered regulation of autoimmunity. 2513 41