Inhaled Particulate Matter Causes Expression of Nuclear Factor (NF)- κ B–Related Genes and Oxidant-Dependent NF- κ B ActivationIn Vitro

Abstract

High levels of ambient air pollution are associated with exacerbation of asthma and respiratory morbidity, yet little is known concerning the mechanisms of inflammation and toxicity by components of inhaled particulate matter (PM). Brief inhalation of PM(2.5) (particles of an aerodynamic diameter of < 2.5 microns) (300 microg/m(3) air for 6 h followed by a period of 24 h in clean air) by either C3H/HeJ or C57/BL6 mice caused significant (P </= 0.05) increases in steady-state messenger RNA (mRNA) levels of a number of nuclear factor (NF)-kappaB-associated and/ or -regulated genes, including tumor necrosis factor-alpha and -beta, interleukin-6, interferon-gamma, and transforming growth factor-beta. Lung mRNA levels of lymphotoxin-beta and macrophage migration inhibitory factor were unchanged. In murine C10 alveolar cells and an NF-kappaB-luciferase reporter cell line, exposure to PM(2.5) at noncytotoxic concentrations resulted in increases in transcriptional activation of NF-kappaB-dependent gene expression which were inhibited in the presence of catalase. Early and persistent increases in intracellular oxidants, as measured by flow cytometry and cell imaging using the oxidant probe 2'-7'-dichlorofluoroscin diacetate, were observed in epithelial cells exposed to PM(2.5) and ultrafine carbon black particles. Studies here are the first to show NF-kappaB-related inflammatory and cytokine gene expression after inhalation of PM(2.5) and oxidant-dependent induction of NF-kappaB activity by PM(2.5) in pulmonary epithelial cells.

Air pollution, oxidative stress and dietary supplementation: a review

“…In addition, target cells, such as airway epithelial cells and macrophages, generate ROS in response to particle uptake by biologically catalysed oxidation reactions that occur in the cell membrane and mitochondria [4,[40][41][42]. In vitro studies have shown that inhaled PM causes expression of nuclear factor (NF)-kB-related genes and oxidant-dependent NF-kB activation [43,44]. The dose of bio-available transition metal, rather than particulate mass, may be the primary determinant of acute inflammatory response [35,37,44].…”

“…In vitro studies have shown that inhaled PM causes expression of nuclear factor (NF)-kB-related genes and oxidant-dependent NF-kB activation [43,44]. The dose of bio-available transition metal, rather than particulate mass, may be the primary determinant of acute inflammatory response [35,37,44]. However, other studies suggest that the hydrosoluble fraction is responsible for the oxidative damage to DNA [45].…”

“…At higher exposure, the transcription NF-kB and activator protein-1 responses would be activated. This would lead to NF-kB and mitogen-activated protein kinase signalling, altering the function of mitochondria or NADPH, and to increased expression of pro-inflammatory cytokines (such as TNF-a and IL-8 and IL-6) and genes coding adhesion molecules [2,6,15,43,44]. Any enhanced inflammatory response would lead to additional generation of ROS and RNS, together with oxidative DNA damage ( fig.…”

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

“…Gene expression was assessed qualitatively and quantitatively using the MultiProbe RPA system (Riboquant; BD Pharmingen) (21). The murine cytokine template set mCK-5c was used on RNA from 9 day animals (the time of peak inflammation) using radiolabeled antisense RNA probes for Ltn, RANTES, mip-␣, mip-1␤, mip-2, IP-10, mcp-1, tca-3, eotaxin, L32, and gapdh.…”

Pulmonary function tests in Petrol pump workers in Karad town

“…Oxidative stress is induced in these cells 16 . The inflammatory response was studied in mice, in which inhalation of 300 µm 3 of PM 2.5 caused increase in TNF-β, interferon-β, IL-6 and transforming growth factor-β 17 . The carbon particles, the important constituents of PM 10, cause the release of immature neutrophils from the bone marrow, underlining the chief role of PM in pathogenesis of COPD.…”