Silica-Induced Inflammatory Mediators and Pulmonary Fibrosis

Abstract

S ilicosis continues to be a lung disease with significant morbidity and mortality. Although silica-induced lung injury and cell activation and/or death have been investigated over the past several years, basic research continues to reveal the cell: cell and cell: mediator interactions critical to these events. This chapter will emphasize the production and participation of several inflammatory cytokines, mediators and cell processes in the development of silica-induced lung injury and fibrosis. Mediators to be discussed will include TNFa, IFNy, IL-ip, IL-12, IL-18, IL-9, TGFp, MMPs/TIMPs, ROS/RNS, caspases and Fas/FasL in die processes of cell activation, cell proliferation and cell death. The mediator networks and apoptotic pathways elicited by this inorganic particle are complex, driven by many cell types and affect numerous cell functions. Understanding these interactions will help in developing strategies for therapeutic intervention at difierent stages of the disease. Silica and SilicosisIn the United States alone, silicosis was listed as a primary or contributing cause of death in 4313 individuals from [1979][1980][1981][1982][1983][1984][1985][1986][1987][1988][1989][1990].^ With the significant occupational health risk posed by silica exposure, research endeavors to explore the cellular and inflammatory mechanisms underlying silica induced limg injury are critical.

Bosutinib Therapy Ameliorates Lung Inflammation and Fibrosis in Experimental Silicosis

“…This study presents limitations: (1) bosutinib was administered 15 days after silica administration, when the disease was already established, but further studies are required evaluating the effects of bosutinib late in the course of disease; and (2) we did not evaluate the impact of bosutinib on different components of extracellular matrix (ECM), as well as MMP and TIMPS in the lung, but focused on the main component of ECM (collagen fiber) modified in silicosis (Hubbard et al, 2005 ).…”

Unveiling the Variability of “Quartz Hazard” in Light of Recent Toxicological Findings

“…activator protein-1 (AP-1), the activity of a number of soluble and cell-derived mediators, and oxidant-mediated triggering mechanisms, [162][163][164] which will also contribute to the variability in so far as related to some physico-chemical features of the particles. As instance, particle-and cellderived ROS establish a robust oxidant milieu, meanwhile the major antioxidant defenses present in the bronchoalveolar space, ascorbate and glutathione, both react with the quartz surface -with silanols 86 and iron ions, 85 respectively.…”

“…The variability of quartz hazard can be fully justified by the large variations occurring in surface silanol distribution, which implies different levels of inflammation. However, besides inflammasome activation, the inflammatory response to silica is the result of several activated biochemical cascades such as the transcriptional regulators nuclear factor-kB (NF-kB) and activator protein-1 (AP-1), the activity of a number of soluble and cell-derived mediators, and oxidant-mediated triggering mechanisms, − which will also contribute to the variability insofar as related to some physicochemical features of the particles. For instance, particle- and cell-derived ROS establish a robust oxidant milieu; meanwhile, the major antioxidant defenses present in the bronchoalveolar space, ascorbate and glutathione, both react with the quartz surface, with silanols and iron ions, respectively.…”

Hubungan antara Pajanan Debu Silika dengan Transforming Growth Factor-ß1 Serum pada Pekerja Industri Pengolahan Batu

“…5 Gangguan fungsi paru yang ditimbulkan oleh silikosis adalah penurunan kemampuan pengembangan, kapasitas vital, dan kapasitas difusi paru. 7 Selain itu, silikosis juga telah ditemukan berhubungan dengan penyakit paru lainnya seperti tuberkulosis dan kanker paru. 8,9 TGF-ß memiliki peran utama dalam terjadinya fibrosis paru oleh karena kemampuannya untuk menstimulasi proliferasi sel fibroblast dan meningkatkan transkripsi gen yang terlibat dalam sintesis kolagen dan fibronektin.…”