NF-kappaB, a pivotal transcription factor in silica-induced diseases.
Inhalation of silica in a number of occupational settings can result in debilitating and costly lung disease. It is thought that the pathological replacement of functional lung tissue with fibrotic lesions in silica-induced lung disease is the result of chronic inflammation mediated by products of the silica-exposed alveolar macrophage. In particular, inflammatory cytokines, growth factors and reactive oxygen species have been implicated in many acute and chronic inflammatory lung diseases. Pharmacological intervention to modify the production of these mediators has been shown to ameliorate several of these disease processes. Recent studies have demonstrated that the production of these inflammatory mediators is altered as a result of the activation of nuclear factor-kappaB (NF-kappaB). NF-kappaB is a pivotal transcription factor activated by silica in macrophages and other types of lung cells. The understanding of how silica induces NF-kappaB activation and what signaling pathways are involved in this silica-induced NF-kappaB activation is important and should provide valuable new information related to both the etiology and potential treatment of silica-related lung diseases. This review summarizes the molecular mechanisms involved in silica-induced NF-kappaB activation and discusses the importance of NF-kappaB as a critical transcription factor in mediating silica-induced lung diseases.
Chen
Fei
F
The Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Shi
Xianglin
X
D000818:Animals; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism; D012822:Silicon Dioxide / Q000009:adverse effects* / Q000494:pharmacology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D012822:Silicon Dioxide