Oxidative stress and endocytosis are involved in upregulation of interleukin-8 expression in airway cells exposed to PM2.5

Abstract

Inhaled PM2.5 (particulate matter with an aerodynamic diameter of 2.5 μm or less) can induce lung inflammation through released inflammatory mediators from airway cells, such as interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α). However, the mechanisms underlying PM2.5-induced IL-8 gene expression have not been fully characterized. BEAS-2B cells (a human bronchial epithelial cell line) and THP-1 cells (a human macrophage-like cell line) were used as the in vitro models to investigate the underlying mechanism in this study. IL-8 expression was increased in the cells treated with PM2.5 in a dose-dependent manner. The water-soluble and insoluble fractions of PM2.5 suspension were both shown to induce IL-8 expression. PM2.5 exposure could obviously induce ROS (reactive oxygen species) generation, indicative of oxidative stress. Pretreatment with the antioxidant N-acetyl-l-cysteine (NAC) potently inhibited PM2.5-induced IL-8 expression. Employment of the transition metal chelators including TPEN (N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine) or DFO (desferrioxamine) inhibited IL-8 expression induced by PM2.5 by over 20% in BEAS-2B cells, but had minimal effect in THP-1 cells. Pretreatment with the endocytosis inhibitor CytD markedly blocked IL-8 expression induced by PM2.5 in both BEAS-2B and THP-1 cells. In summary, exposure to PM2.5 induced IL-8 gene expression through oxidative stress induction and endocytosis in airway cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1869-1878, 2016.

Insights in particulate matter‐induced allergic airway inflammation: Focus on the epithelium

“…Endocytotic uptake mechanisms or activation of PPR, for instance, are required for the induction of airway epithelial cytokine release upon PM exposure. Addition of CytoD, an inhibitor of actin‐dependent uptake mechanisms, resulted in a significant reduction in PM‐induced IL‐8 and GM‐CSF levels, whereas a blocking antibody to TLR2 inhibited the PM‐induced IL‐8 expression . Moreover, DEPs‐induced IL‐8 and GM‐CSF release were blocked by neutralizing antibodies towards EGFR or autocrine ligands of the EGFR, indicating that activation of the EGFR is an important pathway in DEPs‐induced cytokine release .…”

“…Importantly, after internalization or PRR activation, exposure to ambient PM/DEPs will activate oxidative stress responses in the airway epithelial cells. When lung epithelial cells are exposed to ambient PM/DEPs higher levels of intracellular ROS formation, activation of oxidative stress‐responsive genes, such as HMOX1, and oxidative damage has been demonstrated . Ambient PM/DEPs exposure was further associated with the overexpression of several genes and increased phosphorylated proteins related to the MAPK or PI3K/AKT pathway .…”

“…By extracting ambient PM or DEPs, for instance, it was demonstrated that especially the organic compounds were the main contributors to epithelial IL‐1β, IL‐6, IL‐8 and GM‐CSF release . Moreover, employment of metal chelators led to a significant decrease in IL‐1α, IL‐8 and GM‐CSF expression, indicative for the contribution of metals in cytokine production . Removal of surface‐bound endotoxins led to decreased cytokine responses, that is IL‐1α and GM‐CSF, implicating endotoxins in the PM‐induced epithelial cytokine release.…”

In vitro exposure to isoprene-derived secondary organic aerosol by direct deposition and its effects on <i>COX-2</i> and <i>IL-8</i> gene expression

“…Following the discovery of the potential importance of isoprene SOA in generating ROS, Lin et al (2016) showed that isoprene SOA formed from the reactive uptake of epoxides alters levels of oxidative stress-associated genes, including COX-2 in human lung cells. Oxidative stress caused by ROS plays a major role in lung inflammation and the induction of oxidative stress can lead to IL-8 expression (Tao et al, 2003;Yan et al, 2015). Specifically, oxidants can activate the transcription factor NF-κB, which regulates a wide range of inflammatory genes including IL-8 and COX-2 (Barnes and Adcock, 1997; Schreck et al, 1992).…”

Heavy metals bound to fine particulate matter from northern China induce season-dependent health risks: A study based on myocardial toxicity

“…The oxidative stress induced by excessive levels of ROS could cause further induction of inflammatory mediators, DNA damage and apoptosis. These effects may cause downstream molecular events that trigger vasculature permeabilization and, eventually, cardiovascular disorders (Yan et al, 2015;Tseng et al, 2016). There are some fragmentary studies that have also indicated that the association between PMassociated metals and biological processes is related to oxidative stress and other biological processes.…”