Effect of Nitrogen Dioxide on Synthesis of Inflammatory Cytokines Expressed by Human Bronchial Epithelial Cells In Vitro

Abstract

Although studies of nitrogen dioxide (NO2) inhalation, in both animals and humans, have demonstrated that this agent can cause epithelial cell damage and inflammation of the airway epithelium, the mechanisms underlying these effects are not well understood. We have cultured human bronchial epithelial cells, as explant cultures from surgical tissue, and studied these firstly from their ability to constitutively synthesize specific proinflammatory cytokines and then investigated the effect of exposure to NO2 on the generation of these cytokines. Constitutive synthesis of cytokines was evaluated by analysis of both the expression of the mRNA for interleukin (IL)-1 beta, IL-4, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), by the polymerase chain reaction (PCR), and by immunocytochemical staining for the presence of cell-associated IL-1 beta, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, using specific monoclonal and polyclonal antibodies directed towards these cytokines. Release of IL-4, IL-8, GM-CSF, TNF-alpha, and IFN-gamma following exposure to 5% CO2 in air or 400 ppb and 800 ppb NO2 for 6 h was investigated by enzyme-linked immunosorbent assay. PCR demonstrated that the human bronchial epithelial cells expressed the mRNA for IL-1 beta, IL-8, GM-CSF, and TNF-alpha but not for IL-4 and IFN-gamma. Immunocytochemical staining confirmed the presence of endogenous IL-1 beta, IL-8, GM-CSF, and TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

“…Air pollutants act by increasing airway epithelial barrier permeability, inhibiting mucociliary clearance, and inducing AECs to secrete an array of inflammatory mediators such as chemokines, cytokines, eicosanoids, and adhesion molecules that recruit and activate DCs, ILC2s, and basophils, thus contributing to T H 2-type immunity. O 3 increases the release of IL-8, GM-CSF, TNF-α, and sICAM-1 on cultured human bronchial epithelial cells [112], while NO 2 enhances the secretion of leukotriene C4, CXCL8, GM-CSF, and TNF-α [113,114]. Moreover, diesel exhaust particles upregulate the mRNA levels of TSLP [115], which can promote maturation of myeloid DCs that support T H 2-type polarization [116].…”

Bacterial-induced release of inflammatory mediators by bronchial epithelial cells

“…Studies from our laboratory have demonstrated that human airway epithelial cells are capable of expressing and generating specific cytokines, including IL-6, IL-8 and TNF-α, which may play a role in activation and migration of neutrophils to sites of inflammation in the epithelium [31]. IL-6 is important in the induction of the acute phase response, augmentation of antibody production, and is released relatively early in the inflammatory response [32].…”

Air Pollution Exposure and Osteoporosis among Retired Workers with Chronic Obstructive Pulmonary Disease

“…Our finding provides epidemiological evidence to support the hypothesized mechanisms of air pollution effects on osteoporosis risk through inflammatory responses. Previous findings of epidemiological [15] and toxicological [16] studies on NO 2 demonstrate that pulmonary inflammation is a possible mechanism to explain the association between short-term exposure to NO 2 and cardiovascular effects. Long-term exposure to air pollution has been reported to be associated with elevated interleukin 6 (IL-6), neutrophils [17] and C-reactive protein (CRP) [18,19] in previous studies.…”