Bringing TRAP and NLRP3 into focus to Save EJ Populations

Abstract

• BACKGROUND AND AIMS Whole city studies, especially in cooler climates in advanced economies, have found profoundly large chronic health effects for those living short distances from large regional transportation related air pollution and noise sources, such as busy roadways, relative to similar populations living a kilometer or more from these exposures. (Oslo, Stockholm, Vancouver, Toronto, Boston, Copenhagen). While primary pollutants like ultrafine particles and noise have steep gradients next to large TRAP sources, akin to these health effects, regional pollutants like PM2.5 and ozone have flat or inverse gradients. The spatiotemporal granularity of research required to show these TRAP relationships is more challenging than regional studies keyed on PM2.5 or Ozone (Six Cities vs CAFEH). • METHODS We conducted a literature review of NLRP3 inflammasome and particulates. • RESULTS and CONCLUSIONS Both ambient particulate matter and NLRP3 inflammasome biology, specifically, have been shown to accelerate many major diseases of inflammation – sterile and pathogenic. Inflammasomes generate Interleukin 1 family cytokines such as IL-1beta. Of the 21 human inflammasomes, only NLRP3 reacts strongly to exogenous and endogenous particles. NLRP3 drives the health effects of a broad array of exogenous particles, including manufactured adjuvants, medical imaging agents, mineral fibres and ambient TRAP. And of endogenous particles such as crystalized uric acid, amyloid tau tangles, cholesterol and high molecular weight fatty acids. Environmental justice (EJ) populations tend to concentrate in locations with high TRAP exposures. Without more focused research into environmental justice exposures, that integrates spatiotemporal knowledge of TRAP with NLRP3 immunology, we will be unable to protect these EJ populations. NLRP3 inflammasome biology may be the missing link between TRAP and EJ populations. • KEYWORDS Near source exposures, transportation related air pollution, NLRP3 inflammasome biology, high exposure environmental justice populations