Induction of gene expression by environmental oxidants associated with inflammation, fibrogenesis, and carcinogenesis.
Janssen YM; Timblin CR; Zanella CL; Jimenez LA; Mossman BT
Oxidative Stress and Signal Transduction 1996; :387-414
Induction of gene expression by mineral dusts and other oxidants capable of inducing inflammatory, fibrogenic, and carcinogenic responses was reviewed. The review described the characteristics of genes that play important roles in cell proliferation and discussed stress response genes, genes important in inducing inflammatory responses, cellular defense mechanisms against environmental agents that induce oxidative stress, gene expression involved in apoptosis, and considered signal transduction pathways involved in the induction of inflammatory processes by mineral dusts. A number of experimental studies have shown that mineral dusts such as asbestos (1332214) and crystalline silica (14808607) induce oxidative stress through inflammatory processes involving the cooperative action of various cytokines and chemokines. Signals generated extracellularly at the cell surface by these agents or by oxidants acting as second messengers can proceed along various pathways to induce a change in the phosphorylation status of transcription factors. This may then activate or inactivate transcription factors that will induce changes in gene expression that will culminate in endpoints such as apoptosis, fibrogenesis, or carcinogenesis. A nuclear transcription factor kappa B (NF-kappaB) dependent pathway appears to be the major mechanism underlying the inflammatory response that is observed in asbestos and crystalline silica induced pulmonary disease. NF-kappaB is a transcription factor involved in activation of genes that are involved in cell proliferation and inflammation. Many genes have NF- kappaB sites in their promoter regions that can be involved in gene expression.
NIOSH-Grant; Pulmonary-system-disorders; Cancer; Mineral-dusts; Oxidative-processes; Physiological-stress; Cell-function; Genetics; Cell-division; Fibrogenicity; Respiratory-system-disorders
Pathology University of Vermont Medical Alumni Bldg Burlington, VT 05405
Oxidative Stress and Signal Transduction
University of Vermont & St Agric College, Burlington, Vermont