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

There is evidence that, following exposure to crystalline silica, the release of several proinflammatory cytokines contributes to the induction of unbalanced inflammatory reaction leading to lung fibrosis. We have examined the potential contribution of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the development of silicosis. In a mouse model of inflammatory lung reaction induced by intratracheal instillation of silica (0.5 mg and 5 mg DQ12/mouse), the levels of IL-10 protein (determined by ELISA) both in cells obtained after bronchoalveolar lavage (BAL) and in lung tissue homogenates were significantly increased when compared with controls. After in vitro lipopolysaccharide (LPS) stimulation (1 microg/ml), BAL cells obtained from silica-treated animals produced significantly more IL-10 protein and mRNA than cells obtained from control animals. To examine the role of IL-10 in the lung reaction induced by silica, IL-10-deficient animals were instilled with 5 mg of silica. Twenty-four hours after treatment, the amplitude of the inflammatory response (lactate dehydrogenase [LDH], protein and number of inflammatory cells in BAL) was significantly greater in IL-10-deficient animals than in the wild type. In contrast, the fibrotic response, evaluated by measuring lung hydroxyproline content and by histopathologic analysis 30 days after silica, was significantly less important in IL-10-deficient than in wild-type mice. Together, these data suggest that increased IL-10 synthesis induced by silica can limit the amplitude of the inflammatory reaction, but also contributes to amplify the lung fibrotic response.
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PMID:Role of interleukin-10 in the lung response to silica in mice. 944 45

We previously described a reduction of silica-induced lung fibrosis in interleukin-10-deficient mice (IL-10-/-) (Huaux and colleagues; Am. J. Respir. Cell Mol. Biol. 1998;18:51-59). In the present study, we further dissect the exact functions of IL-10 in experimental silicosis. The reduced lung fibrotic response to silica in IL-10-/- mice was accompanied by a marked recruitment of TH1 CD4+ lymphocytes. However, treatment with anti-CD4 antibodies reduced silica-induced lung fibrosis in both IL-10-/- and IL-10+/+ mice, suggesting that this T cell population actually contributes to the extension of the fibrotic lesions in a manner that is independent of IL-10. In IL-10-/- mice, silica-induced lung production of the profibrotic mediator transforming growth factor (TGF)-beta1 and the antifibrotic eicosanoid PGE2 were reduced and increased, respectively, relative to that in IL-10+/+ mice. In addition, in vitro experiments indicated that recombinant IL-10 upregulated TGF-beta1 expression in alveolar macrophages while in contrast it downregulated PGE2 production and cyclooxygenase-2 expression in both lung fibroblasts and macrophages. Thus the net profibrotic activity of IL-10 in vivo appears to be mediated by its ability to stimulate the expression of the profibrotic cytokine TGF-beta1 while suppressing the expression of cyclooxygenase-2 and thus production of the antifibrotic eicosanoid PGE2. These effects appear to be independent of the enhanced lung CD4+ T-lymphocytosis observed in IL-10-deficient mice.
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PMID:Characterization of the effect of interleukin-10 on silica-induced lung fibrosis in mice. 1497 40

Silicosis is a fibrotic lung disease produced by the inhalation and deposition of silica dust. The association between silicosis and pulmonary tuberculosis (PTB) has been well established. Cytokines participate in the development and progression of silicosis and PTB. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at position -308; in the transforming growth factor-beta 1 (TGF-beta1) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1,082, -819 and -592; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with silicosis and PTB. We conducted a case-control study with 183 silicosis patients and 111 silica-exposed miners, and a 1:2 matched case-control study of 61 PTB cases and 122 PTB-free miners. Genotype analysis was performed on genomic DNA, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. There was complete linkage disequilibrium (LD) between the -819C and -592C alleles of the IL-10 gene. The genotype frequencies were similar between cases and control subjects for all investigated cytokine polymorphisms (p>0.05). We did not find an association between the different genotypes and severity of silicosis. We assume that these genetic variants do not play a dominant role in silicosis and PTB in our Chinese population.
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PMID:Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners. 1893 63