Abstract
In recent years, particle research has focused on activation pathways of transcription factors that are known to regulate genes whose abnormal expression is associated with the pathogenesis of particle-associated lung disorders such as fibrosis, cancer, COPD, and asthma. This article reviews the effects of different particles and fibers on the transcriptional activation of nuclear factor kappa-B (NF-kB), which is involved in the activation of a variety of proinflammatory genes. Particulates that have been found to activate NF-κB, include asbestos, man-made fibers, quartz, and ambient particulates, such as residual oil fly ashes (ROFA) and diesel exhaust particles (DEP). In line with this, a number of NF-κB-regulated genes have been found to be upregulated, such as tumour necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), the interleukins IL-6 and IL-8, cyclooxygenase- II (COX-II), and inducible nitric oxide synthase (iNOS). Important mechanisms involved in the activation of NF-kB by particles or fibers include a role for reactive oxygen species, arachidonic acid metabolism, and particle- or fiber-specific physiochemical properties (e.g., transition metals, fiber dimensions) in processes such as lipid peroxidation and (frustrated) phagocytosis. Intracellularly, NF-κB may be activated via several pathways, for example, involving protein kinase C, tyrosine kinase, or calpain. Future research on NF-κB activation by particles or fibers should aim to further identify these and other pathways and to determine the in vivo significance of this activation in the pathogenesis of lung disease.