Ozone Enhances Pulmonary Innate Immune Response to a Toll-Like Receptor–2 Agonist

Oakes, Judy; O’Connor, Brian P.; Warg, Laura A.; Burton, Rachel A.; Hock, Ashley; Loader, Joan E.; LaFlamme, Daniel; Jing, Jian; Hui, Lucy; Schwartz, David A.; Yang, Ivana V.

doi:10.1165/rcmb.2012-0187oc

Cited by 31 publications

(18 citation statements)

References 46 publications

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“…PM 2.5 likely shares mechanistic pathways with cigarette smoke exposure, which induces small airways constriction by stimulating endothelin release and via direct oxidant effects (42). O 3 exposure has been found to prime innate immunity and up-regulate expression of injury repair genes in mouse lung (43). There is also a neurological component of the acute pulmonary response to O 3 , involving increased excitability of pulmonary afferent C fibers, an effect that may be exerted directly by O 3 or via inflammatory pathways (44,45).…”

Section: Discussionmentioning

confidence: 99%

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

Rice

Ljungman²,

Wilker³

et al. 2013

Am J Respir Crit Care Med

172

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Rationale: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards. Objectives: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study. Methods: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995Massachusetts (5,358 examinations, -2011) who were not current smokers, with previousday pollutant levels in compliance with EPA standards. We compared lung function (FEV 1 and FVC) after previous-day exposure to particulate matter less than 2.5 mm in diameter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) in the "moderate" range of the EPA Air Quality Index to exposure in the "good" range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function. Measurements and Main Results: Exposure to pollutant concentrations in the "moderate" range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV 1 for PM 2.5 (95% confidence interval [CI], 233.4, 26.9), a 30.6-ml lower FEV 1 for NO 2 (95% CI, 260.9, 20.2), and a 55.7-ml lower FEV 1 for O 3 (95% CI, 2100.7, 210.8) compared with the "good" range. The 1-and 2-day moving averages of PM 2.5 , NO 2 , and O 3 before testing were negatively associated with FEV 1 and FVC.Conclusions: Short-term exposure to PM 2.5 , NO 2 , and O 3 within current EPA standards was associated with lower lung function in this cohort of adults.Keywords: chronic obstructive pulmonary disease; asthma; air pollutants; U.S. Environmental Protection Agency A substantial body of evidence has shown that modest shortterm increases in ambient air pollution, especially PM 2.5 (particles with an aerodynamic diameter < 2.5 mm) and ground level ozone (O 3 ), but also nitrogen dioxide (NO 2 ), increase risk of hospitalization for chronic obstructive pulmonary disease (COPD) and respiratory mortality (1-4). Several studies have found that short-term (1-3 d) increases in PM 2.5 , NO 2 , and O 3 are associated with decreases in FEV 1 , FVC, and/or peak expiratory flow rate in healthy subjects (5-11) and in those with preexisting COPD or asthma (12)(13)(14)(15).Air quality has improved substantially since the 1980s and 1990s, when many epidemiologic investigations of lung function and air pollution were completed (16). To protect public health and in accordance with its mandate, the EPA has continued to review the latest evidence and reevaluate air quality standards. Recently, the EPA lowered the annual standard for PM 2.5 from 15 to 12 mg/m 3 and reduced the daily Air Quality Index (AQI) cut-off for "moderate" PM 2.5 from 15.4 to 12 mg/m 3 . It remains unclear whether acute effects of criteria air pollutants (inclu...

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Section: Discussionmentioning

confidence: 99%

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

Rice

Ljungman²,

Wilker³

et al. 2013

Am J Respir Crit Care Med

172

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

Rice¹,

Ljungman²,

Wilker³

et al. 2013

ISEE Conference Abstracts

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Rationale: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards. Objectives: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study. Methods: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995 who were not current smokers, with previousday pollutant levels in compliance with EPA standards. We compared lung function (FEV 1 and FVC) after previous-day exposure to particulate matter less than 2.5 mm in diameter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) in the "moderate" range of the EPA Air Quality Index to exposure in the "good" range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function. Measurements and Main Results: Exposure to pollutant concentrations in the "moderate" range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV 1 for PM 2.5 (95% confidence interval [CI], 233.4, 26.9), a 30.6-ml lower FEV 1 for NO 2 (95% CI, 260.9, 20.2), and a 55.7-ml lower FEV 1 for O 3 (95% CI, 2100.7, 210.8) compared with the "good" range. The 1-and 2-day moving averages of PM 2.5 , NO 2 , and O 3 before testing were negatively associated with FEV 1 and FVC.Conclusions: Short-term exposure to PM 2.5 , NO 2 , and O 3 within current EPA standards was associated with lower lung function in this cohort of adults.A substantial body of evidence has shown that modest shortterm increases in ambient air pollution, especially PM 2.5 (particles with an aerodynamic diameter < 2.5 mm) and ground level ozone (O 3 ), but also nitrogen dioxide (NO 2 ), increase risk of hospitalization for chronic obstructive pulmonary disease (COPD) and respiratory mortality (1-4). Several studies have found that short-term (1-3 d) increases in PM 2.5 , NO 2 , and O 3 are associated with decreases in FEV 1 , FVC, and/or peak expiratory flow rate in healthy subjects (5-11) and in those with preexisting COPD or asthma (12)(13)(14)(15).Air quality has improved substantially since the 1980s and 1990s, when many epidemiologic investigations of lung function and air pollution were completed (16). To protect public health and in accordance with its mandate, the EPA has continued to review the latest evidence and reevaluate air quality standards. Recently, the EPA lowered the annual standard for PM 2.5 from 15 to 12 mg/m 3 and reduced the daily Air Quality Index (AQI) cut-off for "moderate" PM 2.5 from 15.4 to 12 mg/m 3 . It remains unclear whether acute effects of criteria air pollutants (including

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“…Since no pathogens are involved, this process is termed "sterile inflammation." Ozone may increase the immune responses to TLR2 in the lungs [39]. Following ozone exposure, macrophages produce pro-inflammatory mediators, e.g., NF-κB, and release cytotoxic substances.…”

Section: Ozonementioning

confidence: 99%

Role of the Toll Like Receptor (TLR) Radical Cycle in Chronic Inflammation: Possible Treatments Targeting the TLR4 Pathway

Lucas¹,

2013

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Activation of the Toll-like receptor 4 (TLR4) complex, a receptor of the innate immune system, may underpin the pathophysiology of many human diseases, including asthma, cardiovascular disorder, diabetes, obesity, metabolic syndrome, autoimmune disorders, neuroinflammatory disorders, schizophrenia, bipolar disorder, autism, clinical depression, chronic fatigue syndrome, alcohol abuse, and toluene inhalation. TLRs are pattern recognition receptors that recognize damage-associated molecular patterns and pathogen-associated molecular patterns, including lipopolysaccharide (LPS) from gram-negative bacteria. Here we focus on the environmental factors, which are known to trigger TLR4, e.g., ozone, atmosphere particulate matter, long-lived reactive oxygen intermediate, pentachlorophenol, ionizing radiation, and toluene. Activation of the TLR4 pathways may cause chronic inflammation and increased production of reactive oxygen and nitrogen species (ROS/RNS) and oxidative and nitrosative stress and therefore TLR-related diseases. This implies that drugs or substances that modify these pathways may prevent or improve the abovementioned diseases. Here we review some of the most promising drugs and agents that have the potential to attenuate TLR-mediated inflammation, e.g., anti-LPS strategies that aim to neutralize LPS (synthetic anti-LPS peptides and recombinant factor C) and TLR4/MyD88 antagonists, including eritoran, CyP, EM-163, epigallocatechin-3-gallate, 6-shogaol, cinnamon extract, N-acetylcysteine, melatonin, and molecular hydrogen. The authors posit that activation of the TLR radical (ROS/RNS) cycle is a common pathway underpinning many "civilization" disorders and that targeting the TLR radical cycle may be an effective method to treat many inflammatory disorders.

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Ozone Enhances Pulmonary Innate Immune Response to a Toll-Like Receptor–2 Agonist

Cited by 31 publications

References 46 publications

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

Role of the Toll Like Receptor (TLR) Radical Cycle in Chronic Inflammation: Possible Treatments Targeting the TLR4 Pathway

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