Basic pathogenetic mechanisms in silicosis: current understanding.
OBJECTIVE
Silicosis continues to be a common cause of chronic lung diseases, despite evidence that these diseases can be prevented by environmental dust control. Silicosis has been studied extensively by basic and clinical scientists, yet little is known about the crucial cellular and molecular mechanisms that initiate and propagate the process of inflammation and scarring.


RESULTS
Recent in vivo, in vitro, and human studies have focused on several main areas of investigation into the causes and processes of the development of silicosis. These areas of investigation include the variability of pathogenic potential of different varieties of silica; the role of activated alveolar macrophages products in the development and progression of silicosis; and the direct role played by the silica particle surface in triggering adverse biologic reactions, such as generating ROS and RNS. The generation of oxidants by silica particles and by silica-activated cells results in cell and lung damage; increased expression of inflammatory cytokines, including TNF-alpha, IL 1 beta, and TGF-beta; activation of cell signaling pathways, including the MAP kinase pathways; and phosphorylation and activation of specific transcription factors (e.g., NFkB). The ROS, RNS, and NO generated by the silica particles also induce apoptosis in macrophages and other cells.


CONCLUSIONS
Further research on the molecular mechanisms involved in the inflammatory processes important for progression to fibrotic diseases is needed for the development of effective treatment of silicosis. Potential therapeutic strategies include inhibition of cytokines such as IL-1, TNF alpha, the use of anti-oxidants, and the inhibition of apoptosis.
Rimal
Binaya
B
Division of Pulmonary and Critical Care Medicine, NYU School of Medicine, New York, New York 10016, USA.
Greenberg
Alissa K
AK
Rom
William N
WN
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000473:pathology; D051379:Mice; D009336:Necrosis; D018384:Oxidative Stress; D010587:Phagocytosis; D051381:Rats; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D012822:Silicon Dioxide