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.

This review is partly composed of the presentation "Cytokine alteration and speculated immunological pathophysiology in silicosis and asbestos-related diseases" delivered during the symposium "Biological effects of fibrous and particulate substances and related areas" organized by the Study Group of Fibrous and Particulate Studies of the Japanese Society of Hygiene and held at the 78th Annual Meeting in Kumamoto, Japan. In this review, we briefly introduce the results of recent immunological analysis using the plasma of silica and asbestos-exposed patients diagnosed with silicosis, pleural plaque, or malignant mesothelioma. Thereafter, experimental background and speculation concerning the immunological pathophysiology of silica and asbestos-exposed patients are discussed.

It is common knowledge that exposure to asbestos causes asbestos-related diseases, such as asbestosis, lung cancer and malignant mesothelioma, not only in people who have had long-term contact with asbestos in their work environment but also in residents living near factories that handle asbestos. Since the summer of 2005, these revelations turned into a large medical problem and caused and social unrest. We have focused on the immunological effects of both asbestos and silica on the human immune system. In this brief review, we introduce immunological alterations found in patients with malignant mesothelioma and describe the experimental background in which these were found. Analyzing the immunological effects of asbestos may improve our understanding of the biological effects of asbestos.

OBJECTIVEDocosahexaenoic acid (DHA) is known as a chemopreventive substance for cancers. Previously we reported that DHA induces apoptosis in HL-60 cells. The aim of this study was to clarify the role of phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling during DHA-induced apoptosis in HL-60 cells.

METHODSThe inhibitory effects of dibutyryl cAMP (db-cAMP) or LY294002 (a specific inhibitor of the PI3-kinase/Akt pathway) on DHA-induced apoptosis in HL-60 cells were evaluated by the appearance of apoptosis, and from the activities of caspases (3 and 8), the phospholylation of Akt, and cleavage of Bid using DNA indexes, emzymatic measurement of fragmented substrates, and Western blotting, respectively.

RESULTSThe pre-incubation of db-cAMP reduced the activation of caspasses (3 and 8) during the occurrence of DHA-induced apoptosis in HL-60. However, the inhibition of PI3-kinase/Akt signaling by LY294002 resulted in recovery of the caspases' activities, appearance of apoptotic cells, and cleavage of the Bid molecule when LY294002 was co-treated with db-cAMP before the occurrence of DHA-induced apoptosis in HL-60. It was also confirmed that LY294002 strongly inhibited phospholylation of Akt during db-cAMP induced-reduction of DHA-induced apoptosis in HL-60.

CONCLUSIONWe demonstrated that DHA-induced apoptosis was sensitive to the modulation of PI3-kinase activity by treatment with db-cAMP or LY294002. These results may provide new insights into the mechanisms of the anti-cancer activity of DHA.

Objectives: Several studies have reported that the secretory immunoglobulin A (S-IgA) concentration in saliva is an indicator of psychological stress. The aim of this study was to clarify the relationship between S-IgA and the stress from academic examinations. Methods: S-IgA levels in 10 medical student volunteers from the second year course between May 4 and July 13, 2000 were examined using the ELISA method. Results: There was a tendency for S-IgA in saliva to be higher on the day before academic examinations and during them, and lower on the days between these examinations. Conclusions: It may be possible to use this measurement to monitor psychological stress in students and workers.
Upper case ess ; Immunoglobulin A measurement ; Saliva ; Stress bismuth subsalicylate ; Daily

OBJECTIVESThe aim of this study was to detect anti-topoisomerase I (anti-topo I) autoantibodies, which are known to be limited in systemic sclerosis patients, in silicosis patients with no clinical symptoms of autoimmune disease.

METHODSSerum anti-topo I autoantibodies were detected using ELISA. Differences in clinical parameters between patients with and without anti-topo I autoantibodies were analyzed.

RESULTSSeven of 69 patients had anti-topo I autoantibodies. These 7 patients showed elevated PaCO(2) values (P=0.0212), and inverse correlations between serum soluble Fas levels and PaCO(2) values were found.

CONCLUSIONAnti-topo I autoantibodies were detected in 10.1% of silicosis patients without any clinical symptoms of autoimmune disease. The findings here suggest that the genesis of anti-topo I autoantibodies might be related to pulmonary involvement or lung fibrosis associated with progression of silicosis.