Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells

Background: Exposure to ambient air particulate matter (PM) has been shown to increase rates of cardiopulmonary morbidity and mortality, but the underlying mechanisms are still not well understood

Short-term effects of air temperature on blood markers of coagulation and inflammation in potentially susceptible individuals.

Objectives Changes in air temperature are associated with an increase in cardiovascular events, but the role of procoagulant and proinflammatory blood markers is still poorly understood. The authors investigated the association between air temperature and fibrinogen, plasminogen activator inhibitor type 1, interleukin-6 and high-sensitivity C reactive protein in two potentially susceptible groups. Methods This prospective panel study was conducted between March 2007 and December 2008 in Augsburg, Germany. The study population comprised 187 participants with type 2 diabetes mellitus or impaired glucose tolerance and 87 participants with genetic polymorphisms on the detoxification and inflammation pathways. Overall, 1766 repeated blood measurements were collected. Hourly meteorology data were available from a central measurement site. The association between temperature and blood markers was analysed with additive mixed models. Results For type 2 diabetes mellitus and impaired glucose tolerance participants, the authors observed immediate, lagged and cumulative increases in fibrinogen (range of percentage changes in geometric mean: 0.6%-0.8%) and plasminogen activator inhibitor type 1 (6.0%-10.1%) in association with a 5 degrees C temperature decrement. Participants with a body mass index above 30 kg/m(2) as well as females showed particularly strong fibrinogen effects. In participants with the special genetic background, 5 degrees C decreases in the 5-day average of temperature led to a change of 8.0% (95% CI 0.5% to 16.2%) in interleukin-6 and of -8.4% (95% CI - 15.8% to -0.3%) in high-sensitivity C reactive protein, the latter driven by physically active individuals. Conclusions The authors observed different temperature effects on blood markers in two potentially susceptible groups probably indicating varying underlying biological mechanisms. This study results might provide a link between temperature and cardiovascular events

Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells

Background: Exposure to ambient air particulate matter (PM) has been shown to increase rates of cardiopulmonary morbidity and mortality, but the underlying mechanisms are still not well understood. Objective: We examined signaling events involved in the expression of the inflammatory gene interleukin-8 (IL-8) in human airway epithelial cells (HAECs) exposed to ambient PM collected in an urban area of Mexicali, Mexico. Methods: We studied IL-8 expression and regulatory signaling pathways in cultured HAECs exposed to Mexicali PM suspended in media for 0–4 hr. Results: Exposure resulted in a dose-dependent, 2- to 8-fold increase in IL-8 mRNA expression relative to controls. PM exposure induced IL-8 transcriptional activity in BEAS-2B cells that was dependent on the nuclear factor-kappa B (NF-κB) response element in the IL-8 promoter. Chromatin immunoprecipitation (ChIP) assays showed a 3-fold increase in binding of the p65 (RelA) NF-κB isoform to the IL-8 promoter sequence in HAECs exposed to PM. Western blot analyses showed elevated levels of phosphorylation of p65 but no changes in IκBα phosphorylation or degradation. IL-8 expression was blunted in a dose-dependent manner in BEAS-2B cells transduced with a lentivirus encoding a dominant negative p65 mutant in which phosphorylation sites were inactivated. Conclusion: Taken together, these findings show that the increase in IL-8 mRNA expression in HAECs exposed to PM(10) (PM ≤ 10 μm in aerodynamic diameter) is mediated through an NF-κB–dependent signaling mechanism that occurs through a pathway involving direct phosphorylation of the transcription factor p65 in the absence of IκBα degradation. These data show that exposure to PM(10) in ambient air can induce inflammatory responses by activating specific signaling mechanisms in HAECs