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Thu 9/19/2019 11:00AM - 12:00PM
EOH Journal Club
Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen EOH Journal Club
Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen
Thu 9/19/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Brandy Hill

Paper: Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen. A Randomized, Double-Blind Crossover Study

Authors: Denise J. Wooding, Min Hyung Ryu, Anke Huls, Andrew D. Lee, David T. S. Lin, Christopher F. Rider, Agnes C. Y. Yuen, and Chris Carlsten

Rationale: Diesel exhaust (DE), an established model of trafficrelated
air pollution, contributes significantly to the global burden of
asthma and may augment the effects of allergen inhalation. Newer
diesel particulate-filtering technologies may increaseNO2 emissions,
raising questions regarding their effectiveness in reducing harm from
associated engine output.

Objectives: To assess the effects of DE and allergen coexposure on
lung function, airway responsiveness, and circulating leukocytes, and
determine whether DE particle depletion remediates these effects.

Methods: In this randomized, double-blind crossover study, 14
allergen-sensitized participants (9 with airway hyperresponsiveness)
underwent inhaled allergen challenge after 2-hour exposures to DE,
particle-depleted DE (PDDE), or filtered air. The control condition
was inhaled saline after filtered air. Blood sampling and spirometry
were performed before and up to 48 hours after exposures. Airway
responsiveness was evaluated at 24 hours.

Measurements and Main Results: PDDE plus allergen
coexposure impaired lung function more than DE plus allergen,
particularly in those genetically at risk. DE plus allergen and PDDE
plus allergen each increased airway responsiveness in normally
responsive participants.DEplus allergen increased blood neutrophils
and was associated with persistent eosinophilia at 48 hours. DE and
PDDE each increased total peripheral leukocyte counts in a manner
affected by participant genotypes. Changes in peripheral leukocytes
correlated with lung function decline.

Conclusions: Coexposure to DE and allergen impaired lung
function, which was worse after particle depletion (which increased
NO2). Thus, particulates are not necessarily the sole or main
culprit responsible for all harmful effects of DE. Policies and
technologies aimed at protecting public health should be scrutinized
in that regard.
Clinical trial registered with www.clinicaltrials.gov (NCT02017431).

Keywords: diesel exhaust; asthma; filter; genetic susceptibility

4140 Public Health, Young Seminar Room

Recent Events

EOH Journal Club

EOH Journal Club - Fall 2017 - Heng Bai

Thursday 9/14 11:00AM - 12:00PM
EOH Journal Club Seminar - Fall 2017

Date: Thursday September 14, 2017

Time: 11am - 12pm

Presenter: Heng Bai

Paper: Role of subcellular calcium redistribution in regulating apoptosis and autophagy in cadmium-exposed primary rat proximal tubular cells

Authors: Fei Liu, Zi-Fa Li, Zhen-Yong Wang, Lin Wang

Abstract: Ca2+ signaling plays a vital role in regulating apoptosis and autophagy.We previously proved that cytosolic Ca2+ overload is involved in cadmium(Cd)-induced apoptosis in rat proximal tubular (rPT) cells, but the source of elevated cytosolic Ca2+ concentration ([Ca2+]c) and the effect of potential subcellular Ca2+ redistribution on apoptosis and autophagy remain to be elucidated. Firstly, data showed that Cd-induced elevation of [Ca2+]c was primarily generated intracellularly. Moreover, elevations of [Ca2+]c and mitochondrial Ca2+ concentration ([Ca2+]mit) with depletion of endoplasmic reticulum (ER) Ca2+ levels ([Ca2+]ER) were revealed in Cd-treated rPT cells, but this subcellular Ca2+ redistributionwas significantly suppressed by 2-Aminoethoxydiphenyl borate (2-APB). Elevated inositol 1,4,5-trisphosphate (IP3) levels with up-regulated IP3 receptor (IP3R) protein levels were shown in Cd-exposed cells, confirming that IP3R-mediated ER Ca2+ release results in the elevation of [Ca2+]c. Up-regulated sequestosome 1 (p62) protein levels and autophagic flux assay demonstrated that Cd impaired autophagic degradation, while N-acetylcysteine (NAC) markedly attenuated Cd-induced p62 and microtubule- associated protein 1 light chain 3-II (LC3-II) accumulation, implying that the inhibition of autophagic flux was due to oxidative stress. Furthermore, pharmacological modulation of [Ca2+]c with 1,2-Bis (2- aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM) and 2-APB alleviated Cdmediated apoptosis, inhibition of autophagic degradation and subsequent cytotoxicity, while thapsigargin (TG) had the opposite regulatory effect on them. In summary, cytosolic calcium overload originated from IP3R-mediated ER Ca2+ release has a negative impact on Cd nephrotoxicity through its promotion of apoptosis and inhibition of autophagic flux.

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Last Updated On Monday, September 11, 2017 by Orbell, Adam W
Created On Monday, September 11, 2017

AugSeptember 2019Oct

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