Size Fractions of Ambient Particulate Matter Induce Granulocyte Macrophage Colony–Stimulating Factor in Human Bronchial Epithelial Cells by Mitogen-Activated Protein Kinase Pathways

Abstract

Environmental pollutants, including ambient particulate matter (PM), increase respiratory morbidity. Studies of model PM particles, including residual oil fly ash and freshly generated diesel exhaust particles, have demonstrated that PM affects inflammatory airway responses. Neither of these particles completely represents ambient PM, and therefore questions remain about ambient particulates. We hypothesized that ambient PM of different size fractions collected from an urban environment (New York City air), would activate primary culture human bronchial epithelial cells (HBECs). Because of the importance of granulocyte-macrophage colony-stimulating factor (GM-CSF) on inflammatory and immunomodulatory processes, we focused our studies on this cytokine. We demonstrated that the smallest size fraction (ultrafine/fine; < 0.18 micro m) of ambient PM (11 micro g/cm(2)), upregulated GM-CSF production (2-fold increase). The absence of effect of carbon particles of similar size, and the day-to-day variation in response, suggested that the chemical composition, but not the particle itself, was necessary for GM-CSF induction. Activation of the extracellular signal-regulated kinase and the p38 mitogen-activated protein kinase was associated with, and necessary for, GM-CSF release. These studies serve to corroborate and extend those on model particles. Moreover, they emphasize the role of the smallest size ambient particles in airway epithelial cell responses.

Diesel exhaust activates redox-sensitive transcription factors and kinases in human airways

“…Much attention has focused on the capacity of DEP to elicit oxidative stress in the lung as the trigger for upregulating these pathways, specifically the redox-sensitive transcription factors NF-B and activator protein-1 (AP-1). Consistent with this, addition of DEP to bronchial epithelial cell cultures has been shown to induce cytokine production associated with activation of NF-B and AP-1 and their associated upstream MAPKs (2,4,6,7,14,15,18,26,37). Furthermore, treatment of epithelial cells and macrophages with antioxidants has been shown to reduce DEP-induced cytokine production by downregulating the activation of these signaling pathways (6,14,15,18,37).…”

“…Instillation of DE particle (DEP) extracts into the nose has also been shown to increase the production of mucosal T helper type 2 (Th2)-related cytokines in atopic volunteers (10). Similarly, bronchial epithelial and macrophage cell lines, as well as primary cultures of bronchial epithelial cells, have been shown to release a variety of chemokines and cytokines when treated with DEP or their organic extracts (2,4,6,7,14,15,18,26,37). The cellular and molecular mechanisms underlying these inflammatory responses remain unresolved.…”

Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract

“…As has been highlighted by us and many others, air pollutants are toxic in part due to their ability to induce oxidative stress (22,27,47). The generation of reactive oxygen species upon exposure to airborne pollutants causes the activation of the NF-B and MAP kinase pathways, which transcriptionally regulate the production of proinflammatory cytokines by the airway epithelium, which, in turn, initiates a cascade of effects that result in local inflammatory responses (14,34,36). In addition to the exacerbation of existing airway disease, these responses may also predispose to the development of acute cardiovascular events, through the systemic spillover of cytokines and induction of the acute phase response (18).…”

“…Because epinephrine has been reported to suppress cytokine expression by BECs (36), cells were washed with HEPES-buffered saline (Biosource), and fresh epinephrine-free medium was added 24 h before stimulation.…”

Diesel Exhaust Particle-Exposed Human Bronchial Epithelial Cells Induce Dendritic Cell Maturation

“…Alternatively, because AEC are the site of first contact with environmental pollutants and are in close proximity to DC, it is reasonable to suggest that adjuvant signals may be derived from these cells. We and others have previously shown that ambient PM or DEP-treated AEC release chemokines with potential to induce DC migration, and cytokines with the potential to participate in the functional maturation of DC (22)(23)(24)(25)(26). We therefore hypothesized that DEP act as an adjuvant for DC maturation via an effect on AEC in the microenvironment.…”