Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells.

Abstract

Nuclear factor icB (NF-icB) is a transcription factor regulating expression of genes intrinsic to inflammation and cell proliferation-features of asbestos-associated diseases. In studies here, crocidolite asbestos caused protracted and dose-responsive increases in proteins binding to nuclear NF-#cB-binding DNA elements in hamster tracheal epithelial (HTE) cells. This binding was modulated by cellular glutathione levels. Antibodies recognizing p65 and p50 protein members of the NF-icB family revealed these proteins in two of the DNA complexes. Transient transfection assays with a construct containing six NF-icB-binding DNA consensus sites linked to a luciferase reporter gene indicated that asbestos induced transcriptional activation of NF-#cB-dependent genes, an observation that was confirmed by Northern blot analyses for c-myc mRNA levels in HTE cells. Studies suggest that NF-ecB induction by asbestos is a key event in regulation of multiple genes involved in the pathogenesis of asbestos-related lung cancers.

Airway Epithelial NF-κB Activation Modulates Asbestos-Induced Inflammation and Mucin Production In Vivo

“…We have shown previously that asbestos fibers cause activation of the NF-B signaling pathway in airway epithelial cells (8,15). In this study, we reveal that NF-B activation in epithelial cells of the lung modulates their differentiation and chronic proliferation by asbestos, as well as chemokines and cytokines, produced by both epithelial and nonepithelial cells.…”

“…We have shown previously that asbestos fibers cause activation of the NF-B signaling pathway in tracheal epithelial cells in vitro (8) and in lung epithelium after inhalation of asbestos by rats (15).…”

Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-κB and IκB kinase-α in human colorectal cancer epithelial cells

“…NF-kB is an inducible higher eukaryotic transcription factor, which has a pivotal role in the regulation of the expression of many genes involved in immune and inflammatory responses (Sha, 1998;Bowie and O'Neill, 2000), the replication and reactivation of many viruses, in neuronal development and neurodegeneration, and in the control of cell proliferation and apoptosis (Baeuerle and Henkel, 1994;Pahl and Baeuerle, 1995;Baeuerle and Baltimore, 1996;Bowie and O'Neill, 2000). NF-kB can be activated in response to a broad range of stimuli and conditions, including bacterial and viral products, inflammatory cytokines such as IL-1 and tumour necrosis factor (TNF), B-and T-cell mitogens, intracellular stresses such as endoplasmic reticulum overload, and extracellular stresses like asbestos fibres, ultraviolet light and cigarette smoke (Baeuerle and Henkel, 1994;Janssen et al, 1995;Pahl and Baeuerle, 1995;Shen et al, 1996;O'Neil and Kaltschmidt, 1997;Bowie and O'Neill, 2000). NF-kB is present in the cytoplasm of unstimulated cells in a latent form, comprising a transcriptionally active dimer bound to an inhibitory protein, IkB (Sha, 1998).…”

Arsenic alters the function of the glucocorticoid receptor as a transcription factor.

“…The cells were shaken gently at room temperature for 5 min and then scraped and spun at 4°C for 13,600 × g avg for 5 min, and supernatant was isolated as cytosolic protein fraction. The remaining pellet was then processed for nuclear extracts by the procedure of Dignam (17) as modified by Janssen et al (18). Briefly, the pellet was washed with 1.0 mL of buffer A (10 mM HEPES, 0.1 mM EDTA, 0.1 mM EGTA, 10 mM KCl, and 0.01 mM of the protease inhibitor combination) and then spun at 13,600 × g avg for 2 min at 4°C.…”