Cytokine alteration and speculated immunological pathophysiology in silicosis and asbestos-related diseases

Abstract

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.

Exposure to negatively charged-particle dominant air-conditions on human lymphocytes in vitro activates immunological responses

“…After a two-week incubation of PBMCs in experimental or standard incubators, the concentrations of cytokines (interferon (IFN) ␥, IL-10, IL-2, IL-6 and TNF␣) in culture supernatants were measured with the Cytometric Bead Array kit (CBA, BD Bioscience) using FACSCalibur according to the manufacturer's instructions, as reported previously (Takahashi et al, 2008Murakami et al, 2009;Otsuki et al, 2009). …”

Dysregulation of the immune system caused by silica and asbestos

“…One population is a weaker membrane Fas expresser and these cells may have developed out of an excessive transcription of the alternatively-spliced Fas gene and other variant messages. Therefore, these cells may be resistant to the functional anti-Fas autoantibody, secrete higher levels of soluble Fas, DCR3, and spliced variants, and are resistant to Fas-mediated apoptosis (Otsuki et al, 2003Murakami et al, 2009). As reported previously, patients with a weaker MFI of membrane Fas often have a higher titer of anti-nuclear antibodies, and self-recognizing clones in silicosis may be included in the fraction because these clones may survive longer and show resistance to apoptosis.…”

“…This recruited fraction would not have encountered silica and would be sensitive to silica/silicateinduced apoptosis. As a result, cells in this fraction would be continuously undergoing renewal and then apoptosis (Otsuki et al, 2003Murakami et al, 2009). According to recent developments concerning regulation of T-lymphocyte reactions against intrinsic or foreign antigens, a modification of the population (i.e.…”

Silica exposure and altered regulation of autoimmunity

“…Although the biological mechanisms of silica-induced altered regulation of autoimmunity have been considered adjuvant effects of silica particles [15], we have been investigating the supposition that silica particles directly alter the cellular and molecular biological characteristics of immunocompetent cells due to chronic and recurrent encounters at the lung and intra-pulmonary lymph nodes, and that these alterations of immune cells may cause these cells to gradually progress toward the disruption of autoimmune tolerance [16][17][18][19].…”