Diurnal variation in the proinflammatory activity of urban fine particulate matter (PM2.5) by in vitro assays

Abstract

Background: Ambient particulate matter (PM) smaller than 2.5 µm in diameter (PM 2.5) undergoes diurnal changes in chemical composition due to photochemical oxidation. In this study we examine the relationships between oxidative activity and inflammatory responses associated with these diurnal chemical changes. Because secondary PM contains a higher fraction of oxidized PM species, we hypothesized that PM 2.5 collected during afternoon hours would induce a greater inflammatory response than primary, morning PM 2.5. Methods: Time-integrated aqueous slurry samples of ambient PM 2.5 were collected using a direct aerosol-into-liquid collection system during defined morning and afternoon time periods. PM 2.5 samples were collected for 5 weeks in the late summer (August-September) of 2016 at a central Los Angeles site. Morning samples, largely consisting of fresh primary traffic emissions (primary PM), were collected from 6-9am (am-PM 2.5), and afternoon samples were collected from 12-4pm (pm-PM 2.5), when PM composition is dominated by products of photochemical oxidation (secondary PM). The two diurnally phased PM 2.5 slurries (am- and pm-PM 2.5) were characterized for chemical composition and BV-2 microglia were assayed in vitro for oxidative and inflammatory gene responses. Results: Contrary to expectations, the am-PM 2.5 slurry had more proinflammatory activity than the pm-PM 2.5 slurry as revealed by nitric oxide (NO) induction, as well as the upregulation of proinflammatory cytokines IL-1β, IL-6, and CCL2 (MCP-1), as assessed by messenger RNA production. Conclusions: The diurnal differences observed in this study may be in part attributed to the greater content of transition metals and water-insoluble organic carbon (WIOC) of am-PM 2.5 (primary PM) vs. pm-PM 2.5 (secondary PM), as these two classes of compounds can increase PM 2.5 toxicity.

Early life exposure to air pollution impacts neuronal and glial cell function leading to impaired neurodevelopment

“…[45,46] Similar effects were observed in studies of primary rat microglia using a smaller particle size after both acute (<24 h) and chronic (<7 days) treatments [47,48] and in a microglial cell line with acute treatment using PM2.5. [49][50][51] Primary mixed glial cultures and microglial cell line experiments suggest that PM activate proinflammatory gene expression via toll-like receptor 4/NF-κB signaling. [52][53][54][55] Co-cultures of primary microglia with rodent cerebellar granule [45] or cortical [46,56,57] neurons have established that exposure to DEP and/or PM 2.5 (and subsequent proinflammatory cytokine production) reduced neurite outgrowth and increased neurotoxicity by and reduced the expression of proinflammatory cytokines (pioglitazone, minocycline) had neuroprotective roles.…”

“…[ 45,46 ] Similar effects were observed in studies of primary rat microglia using a smaller particle size after both acute (<24 h) and chronic (<7 days) treatments [ 47,48 ] and in a microglial cell line with acute treatment using PM2.5. [ 49–51 ] Primary mixed glial cultures and microglial cell line experiments suggest that PM activate proinflammatory gene expression via toll‐like receptor 4/NF‐κB signaling. [ 52–55 ]…”

“…Moreover, pathway enrichment analysis in pregnant women indicates that maternal oxidative stress-related pathways are altered, ultimately resulting in an increased risk of pregnancy complications. [80] PM exposure results in a dramatic increase in ROS and reactive nitrogen species (RNS) in primary rodent microglia [46,50,55,57] and neurons [51,74] resulting in significant damage to cellular components including proteins, lipids and DNA. Both acute and chronic exposure of adult rodents to inhaled PM 2.5 result in increased oxidative stress markers such as SOD1 and NRF2 in the brain accompanied by lipid peroxidation.…”

Cerebral cortex and blood transcriptome changes in mouse neonates prenatally exposed to air pollution particulate matter

“…Another example is nitric oxide signaling and the potential regulatory role of nitric oxide synthase during nPM-mediated neurotoxicity. Our prior studies showed that nPM induces iNOS, nitric oxide, and/or nitrosylation in cell culture [ 56 , 57 ], hippocampal slice [ 30 ], and in vivo [ 56 ]. Our analyses identified a subset of 322 nPM-DEGs in the female neonatal cerebral cortex after gestational exposure to nPM.…”

Toxicological Effects of Secondary Air Pollutants

“…In a study using PM2.5 collected in the morning and afternoon, more proinflammatory activity as revealed by nitric oxide(NO) induction in cells exposed to morning PM. The upregulation of proinflammatory cytokines IL-1β, IL-6, and CCL2(MCP-1) was observed, which indicated aging reduced toxicity [174] .…”