Detection of alternatively spliced variant messages of Fas gene and mutational screening of Fas and Fas ligand coding regions in peripheral blood mononuclear cells derived from silicosis patients

Otsuki, Takemi; Sakaguchi, Haruko; Tomokuni, A; Aikoh, T; Matsuki, Takakazu; Isozaki, Yumika; Hyodoh, Fuminori; Kawakami, Yasuhiko; Kusaka, Masayasu; Kita, Shoichi; Ueki, Ayako

doi:10.1016/s0165-2478(00)00177-2

Cited by 33 publications

(26 citation statements)

References 28 publications

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“…First, the presence of a DCR3 (or analogue) has been shown to abrograte the ability of FasL to induce inflammatory responses in the lungs of mice (Wortinger et al, 2003). As we noted earlier, the gene expression levels of extracellular inhibitors of FasL binding to receptors (like soluble Fas and DCR3) were higher in PBMC from SPs than in cells from HDs (Otsuki et al, 2000a(Otsuki et al, , b, 2006. Second, an increased presence of transforming growth factor-β (TGF-β) could result in a shift of FasL from an inflammatory to a suppressive function.…”

Section: Disruption Of Tumor Immunity Due To Silicamentioning

confidence: 88%

Dysregulation of the immune system caused by silica and asbestos

Maeda

Nishimura

Kumagai

et al. 2010

Journal of Immunotoxicology

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Section: Disruption Of Tumor Immunity Due To Silicamentioning

confidence: 88%

Dysregulation of the immune system caused by silica and asbestos

Maeda

Nishimura

Kumagai

et al. 2010

Journal of Immunotoxicology

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“…In addition, our previous results indicated that in silicosis patients, who did not manifest clinical signs and symptoms of autoimmune diseases, possessed the dysregulation of Fas-mediated apoptotic pathway in their lymphocytes and was disrupted (5)(6)(7)(8)(9)(10)(11). Therefore, autoimmunity may be affected at the cellular level in these patients.…”

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confidence: 99%

Reduced Function of CD4+25+ Regulatory T Cell Fraction in Silicosis Patients

Wu¹,

Miura²,

Hyodoh³

et al. 2006

Int J Immunopathol Pharmacol

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The quality and quantity of CD4+25+ regulatory T cells (Treg) in silicosis patients (SIL) were examined and' compared with results from healthy donors (HD) because SIL often develop autoimmune diseases along with pulmonary disorders. Peripheral blood mononuclear cells from 57 SIL and 50 HD were analyzed for Treg. Treg frequency and clinical parameters were subjected to a factor analysis. Treg and CD4+25-T cells (Tneg) from five HD and five SIL, sorted by flow-cytometer, were used for functional assays of Treg, the expression pattern of Treg specific genes (FoxP3, GITR and CTLA-4) and activation-related genes (CD122 and CD123). Although the actual frequency of Treg did not differ between SIL and HD, the age-corrected level was reduced in SIL. The factor analysis showed that Treg frequency was positively associated with the serum level of IL-2. The inhibitory effect of Treg on Tneg activation was decreased when the Treg:Tneg ratio was 1:

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“…Although significant mutations in fas and fas ligand coding sequences were not detected, many alternative spliced variants were found and an analysis of amino-acid translation from detected variants showed that all of these as well as the typical soluble fas posses the binding site of the Fas ligand, but lack the transmembrane domain and death domain. These findings indicate that all these variants may inhibit the binding between membrane Fas and the Fas ligand, similar to soluble Fas and DcR3 molecules (37).…”

Section: Alterations Of Fas-related Molecules and Cd4+25+ Regulatory mentioning

confidence: 70%

“…V) The detection of alternatively spliced variants of fas and mutational screening for fas and fas ligand genes were performed (37). Although significant mutations in fas and fas ligand coding sequences were not detected, many alternative spliced variants were found and an analysis of amino-acid translation from detected variants showed that all of these as well as the typical soluble fas posses the binding site of the Fas ligand, but lack the transmembrane domain and death domain.…”

Section: Alterations Of Fas-related Molecules and Cd4+25+ Regulatory mentioning

confidence: 99%

Keynote lecture in the 13th Japanese Society of Immunotoxicology (JSIT 2006)

Otsuki

Miura

Maeda

et al. 2007

Environ Health Prev Med

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Silica and silicates may disturb immune functions such as autoimmunity and tumor immunity, because people who are exposed to the materials sometimes develop autoimmune and malignant diseases, respectively. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition, immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cell-mediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestos-related malignancies is increasing and such malignancies have been a medical and social problem since the summer in 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate the nation wide anxiety about these malignancies.

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Detection of alternatively spliced variant messages of Fas gene and mutational screening of Fas and Fas ligand coding regions in peripheral blood mononuclear cells derived from silicosis patients

Cited by 33 publications

References 28 publications

Dysregulation of the immune system caused by silica and asbestos

Dysregulation of the immune system caused by silica and asbestos

Reduced Function of CD4+25+ Regulatory T Cell Fraction in Silicosis Patients

Keynote lecture in the 13th Japanese Society of Immunotoxicology (JSIT 2006)

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