Nuclear factor Kappa-B activation by particles and fibers

In recent years, particle research has focused on activation pathways of tr anscription factors that are known to regulate genes whose abnormal express ion is associated with the pathogenesis of particle-associated lung disorde r,: such as fibrosis, cancer, COPD, and asthma. Tl,is article reviews the e ffects of different particles and fibers on the transcriptional activation of nuclear factor kappa-B (NF-kappa B), which is involved in the activation of a variety of proinflammatory genes. Particulates that have been found t o activate NF-kappa B, include asbestos, man-made fibers, quartz, and ambie nt particulates, such as residual oil fly ashes (ROFA) and diesel exhaust p articles (DEP). in line with this, a number of NF-kappa B-regulated genes h ave been found to be upregulated, such as tumour necrosis factor-alpha (TNF alpha), macrophage inflammatory protein-2 (MIP-2), the interleukins IL-6 a nd IL-8, cyclooxygenase II (COX-II) and inducible nitric oxide synthase (iN OS). Important mechanisms involved in the activation of NF-kappa B by parti cles 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 peroxidat ion and (frustrated) phagocytosis. Intracellularly, NF-kappa B may be activ ated via several pathways, for example, involving protein kinase C, tyrosin e kinase, or calpain. Future research on NF-kappa B activation by particles or fibers should aim to further identify these and other pathways and to d etermine the in vivo significance of this activation in the pathogenesis of lung disease.