New Insights into Pathomechanisms and Treatment Possibilities for Lung Silicosis

Abstract

Inhalation of silica particles is an environmental and occupational cause of silicosis, a type of pneumoconiosis. Development of the lung silicosis is a unique process in which the vicious cycle of ingestion of inhaled silica particles by alveolar macrophages and their release triggers inflammation, generation of nodular lesions, and irreversible fibrosis. The pathophysiology of silicosis is complex, and interactions between the pathomechanisms have not been completely understood. However, elucidation of silica-induced inflammation cascades and inflammation-fibrosis relations has uncovered several novel possibilities of therapeutic targeting. This article reviews new information on the pathophysiology of silicosis and points out several promising treatment approaches targeting silicosis-related pathways.

Keywords: inflammation; lung fibrosis; oxidative stress; silica; silicosis.

Figure 1

Scheme of major proposed pathomechanisms of pulmonary silicosis. More details about the individual pathomechanisms are provided in the following text. Abbreviations: ATP: adenosine triphosphate, DAMPs: danger-associated molecular patterns, HMGB1: high mobility group box 1 protein, IL: interleukin, K⁺: potassium cations, MAPK: mitogen-activated protein kinase, NF-κB: nuclear factor kappa B, PAMPs: pathogen-associated molecular patterns, PDGF: platelet-derived growth factor, ROS: reactive oxygen species, SR: scavenger receptors, TGFβ: transforming growth factor beta, TLR: Toll-like receptor, TXNIP: thioredoxin-interacting protein.