Chronic Ozone Exposure Research Articles

Histologic, metabolomic, and transcriptomic differences in fir trees from a peri-urban forest under chronic ozone exposure.

Urbanization modifies ecosystem conditions and evolutionary processes. This includes air pollution, mostly as tropospheric ozone (O3), which contributes to the decline of urban and peri-urban forests. A notable case are fir (Abies religiosa) forests in the peripheral mountains southwest of Mexico City, which have been severely affected by O3 pollution since the 1970s. Interestingly, some young individuals exhibiting minimal O3-related damage have been observed within a zone of significant O3 exposure. Using this setting as a natural experiment, we compared asymptomatic and symptomatic individuals of similar age (≤15 years old; n = 10) using histologic, metabolomic, and transcriptomic approaches. Plants were sampled during days of high (170 ppb) and moderate (87 ppb) O3 concentration. Given that there have been reforestation efforts in the region, with plants from different source populations, we first confirmed that all analyzed individuals clustered within the local genetic group when compared to a species-wide panel (Admixture analysis with ~1.5K SNPs). We observed thicker epidermis and more collapsed cells in the palisade parenchyma of needles from symptomatic individuals than from their asymptomatic counterparts, with differences increasing with needle age. Furthermore, symptomatic individuals exhibited lower concentrations of various terpenes (ß-pinene, ß-caryophylene oxide, α-caryophylene, and ß-α-cubebene) than asymptomatic trees, as evidenced through GC-MS. Finally, transcriptomic analyses revealed differential expression for 13 genes related to carbohydrate metabolism, plant defense, and gene regulation. Our results indicate a rapid and contrasting phenotypic response among trees, likely influenced by standing genetic variation and/or plastic mechanisms. They open the door to future evolutionary studies for understanding how O3 tolerance develops in urban environments, and how this knowledge could contribute to forest restoration.

Chronic ozone exposure in mice mimics clinical asthma-COPD overlap syndrome and is attenuated by tiotropium

Chronic ozone exposure in mice mimics clinical asthma-COPD overlap syndrome and is attenuated by tiotropium

Chronic ozone exposure affects nitrogen remobilization in wheat at key growth stages

The interaction between nitrogen storage and translocation, senescence, and late phase photosynthesis is critical to the post-anthesis grain fill period in wheat, but ozone's effect on nitrogen dynamics within the wheat plant is not well understood. This study used solardomes to expose a widely grown elite spring wheat cultivar, cv. Skyfall, to four levels of ozone (30 ppb, 45 ppb, 70 ppb, 85 ppb) for 11 weeks, with two levels of nitrogen fertilization, 140 kg ha−1 and 160 kg ha−1, the higher rate including an additional 20 kg N ha−1 at anthesis. Chronic ozone exposure triggered earlier senescence in the 4th, 3rd and 2nd leaves but not the flag leaf, with a similar pattern of reduced chlorophyll content in the lower, older leaf cohorts, which started before senescence became visible. At anthesis there was no evidence of any effect of ozone on nitrogen storage in upper plant parts. However, high ozone increased levels of residual nitrogen found within plant parts at harvest, with concomitant reductions in C:N ratios and Nitrogen Remobilization Efficiency. Extra nitrogen fertilization applied at anthesis appeared to ameliorate the effect of ozone on nitrogen content and nitrogen translocation. The application of 15N ammonium nitrate at anthesis confirmed that the majority of post-anthesis nitrogen uptake had been translocated to the ear/grain by harvest, with no effect of ozone on the translocation of nitrogen around the plant. These data can inform future modelling of ozone's effect on nitrogen dynamics and global wheat yields.

Chronic Ambient Ozone Exposure Aggravates Autism-Like Symptoms in a Susceptible Mouse Model.

Although there is evidence that exposure to ground-level ozone (O3) may cause an increased risk of neurological disorders (e.g., autistic spectrum disorder), low-dose chronic ozone exposure and its adverse effects on the nervous system have not been fully understood. Here, we evaluated the potential neurotoxic effects of long-term exposure to environmentally relevant O3 concentration (200 μg/m3 via a whole-body inhalation system, 12 h/day for 5 days/week) using a susceptible mouse model of autism induced by valproic acid. Various indicators of oxidative stress, mitochondria, and synapse in the brain tissues were then measured to determine the overall damage of O3 to the mouse brain. The results showed an aggravated risk of autism in mice offspring, which was embodied in decreased antioxidant contents, disturbed energy generation in mitochondria, as well as reduced expressions of protein kinase Mζ (PKMζ) and synaptic proteins [e.g., Synapsin 1 (SYN 1), postsynaptic density protein-95 (PSD-95)]. Overall, our study indicates that prenatal exposure to environmentally relevant O3 may exacerbate the symptoms of autism, shedding light on possible molecular mechanisms and providing valuable insights into the pathogenesis of autism, especially concerning low-dose levels of those pollutants.

Responses of Eight Differentially Heat Sensitive Tomato Cultivars against Chronic Ozone Exposure in the Indo-Gangetic Plain: Growth, Physiology, and Yield

Tropospheric ozone (O3) is an important abiotic stress to plants and its rising concentration adversely affects crop yield. The studies associated with differential responses of tomato (Solanum lycopersicum L.) cultivars to chronic elevated O3 are lacking and need to be further explored for the recognition of O3 resistant cultivars as an adaptive strategy. In the present research, differentially heat sensitive tomato cultivars were treated with elevated O3 (ambient + 20 ppb) to determine their responses by estimating the foliar injury symptoms, variations in growth, physiology, reproductive and yield related attributes. All the tomato cultivars exhibited foliar injury symptoms under elevated O3 treatment, and the intensity of injury corroborated with yield loss. Elevated O3 treatment negatively impacted biomass, growth, physiological and reproductive characteristics of all cultivars. The hierarchal cluster analysis, cumulative stress response index and yield indices differentiated cultivars into sensitive, moderately sensitive and O3 tolerant categories. The thermotolerant, VRT02 and Kashi chayan cultivars (O3 resistant) demonstrated lower yield losses, whereas the thermotolerant (O3 sensitive) Superbug exhibited higher foliar injury, greater alterations in physiology, growth and reproductive traits resulting in greater yield losses than other cultivars. The cultivars with different heat sensitivity did not respond similarly towards O3 stress. Cultivars VRT 02 and Kashi chayan can be recommended for cultivation in areas experiencing high O3 vis-à-vis high temperature conditions.

Quantifying the influence of chronic ozone exposure on global terrestrial ecosystem carbon cycle

Quantifying the influence of chronic ozone exposure on global terrestrial ecosystem carbon cycle

The impact of subchronic ozone exposure on serum metabolome and the mechanisms of abnormal bile acid and arachidonic acid metabolisms in the liver

Ambient ozone (O3) pollution can induce respiratory and cardiovascular toxicity. However, its impact on the metabolome and the underlying mechanisms remain unclear. This study first investigated the serum metabolite changes in rats exposed to 0.5 ppm O3 for 3 months using untargeted metabolomic approach. Results showed chronic ozone exposure significantly altered the serum levels of 34 metabolites with potential increased risk of digestive, respiratory and cardiovascular disease. Moreover, bile acid synthesis and secretion, and arachidonic acid (AA) metabolism became the most prominent affected metabolic pathways after O3 exposure. Further studies on the mechanisms found that the elevated serum toxic bile acid was not due to the increased biosynthesis in the liver, but the reduced reuptake from the portal vein to hepatocytes owing to repressed Ntcp and Oatp1a1, and the decreased bile acid efflux in hepatocytes as a results of inhibited Bsep, Ostalpha and Ostbeta. Meanwhile, decreased expressions of detoxification enzyme of SULT2A1 and the important regulators of FXR, PXR and HNF4α also contributed to the abnormal bile acids. In addition, O3 promoted the conversion of AA into thromboxane A2 (TXA2) and 20-hydroxyarachidonic acid (20-HETE) in the liver by up-regulation of Fads2, Cyp4a and Tbxas1 which resulting in decreased AA and linoleic acid (LA), and increased thromboxane B2 (TXB2) and 20-HETE in the serum. Furthermore, apparent hepatic chronic inflammation, fibrosis and abnormal function were found in ozone-exposed rats. These results indicated chronic ozone exposure could alter serum metabolites by interfering their metabolism in the liver, and inducing liver injury to aggravate metabolic disorders.

Chronic ozone exposure impairs the mineral nutrition of date palm (Phoenix dactylifera) seedlings

Chronic ozone (O3) exposure in the atmosphere preferentially disturbs metabolic processes in the roots rather than the shoot as a consequence of reduced photosynthesis and carbohydrate allocation from the leaves to the roots. The aim of the present study was to elucidate if mineral nutrition is also impaired by chronic O3 exposure. For this purpose, date palm (Phoenix dactylifera) plants were fumigated with ambient, 1.5 × ambient and 2 × ambient O3 in a free air controlled exposure (FACE) system for one growing season and concentrations of major nutrients were analyzed in leaves and roots. In addition, concentrations of C and N and their partitioning between different metabolic C and N pools were determined in both organs. The results showed that calcium (Ca), magnesium (Mg), iron (Fe), zinc (Zn), sodium (Na) and potassium (K) acquisition by roots was diminished by O3 exposure of the shoot. For Ca, Mg, Fe and Zn reduced uptake by the roots was combined with reduced allocation to the shoot, resulting in a decline of foliar concentrations; for Na and K, allocation to the shoot was maintained at the expense of the roots. Thus, elevated O3 impaired both mineral uptake by the roots and partitioning of minerals between roots and shoots, but in an element specific way. Thereby, elevated O3 affected roots and shoots differently already after one growing season. However, considerable changes in total C and N concentrations and their partitioning between different metabolic pools upon chronic O3 exposure were not observed in either leaves or roots, except for reduced foliar lignin concentrations at 2 × ambient O3. Significant differences in these parameters were shown between leaves and roots independent of O3 application. The physiological consequences of the effects of chronic O3 exposure on mineral acquisition and partitioning between leaves and roots are discussed.

Inflammation resolution in environmental pulmonary health and morbidity

Inflammation and resolution are dynamic processes comprised of inflammatory activation and neutrophil influx, followed by mediator catabolism and efferocytosis. These critical pathways ensure a return to homeostasis and promote repair. Over the past decade research has shown that diverse mediators play a role in the active process of resolution. Specialized pro-resolving mediators (SPMs), biosynthesized from fatty acids, are released during inflammation to facilitate resolution and are deficient in a variety of lung disorders. Failed resolution results in remodeling and cellular deposition through pro-fibrotic myofibroblast expansion that irreversibly narrows the airways and worsens lung function. Recent studies indicate environmental exposures may perturb and deregulate critical resolution pathways.Environmental xenobiotics induce lung inflammation and generate reactive metabolites that promote oxidative stress, injuring the respiratory mucosa and impairing gas-exchange. This warrants recognition of xenobiotic associated molecular patterns (XAMPs) as new signals in the field of inflammation biology, as many environmental chemicals generate free radicals capable of initiating the inflammatory response. Recent studies suggest that unresolved, persistent inflammation impacts both resolution pathways and endogenous regulatory mediators, compromising lung function, which over time can progress to chronic lung disease. Chronic ozone (O3) exposure overwhelms successful resolution, and in susceptible individuals promotes asthma onset. The industrial contaminant cadmium (Cd) bioaccumulates in the lung to impair resolution, and recurrent inflammation can result in chronic obstructive pulmonary disease (COPD). Persistent particulate matter (PM) exposure increases systemic cardiopulmonary inflammation, which reduces lung function and can exacerbate asthma, COPD, and idiopathic pulmonary fibrosis (IPF). While recurrent inflammation underlies environmentally induced pulmonary morbidity and may drive the disease process, our understanding of inflammation resolution in this context is limited. This review aims to explore inflammation resolution biology and its role in chronic environmental lung disease(s).

Identifying and modelling key physiological traits that confer tolerance or sensitivity to ozone in winter wheat

Tropospheric ozone threatens crop production in many parts of the world, especially in highly populated countries in economic transition. Crop models suggest substantial global yield losses for wheat, but typically such models fail to address differences in ozone responses between tolerant and sensitive genotypes. Therefore, the purpose of this study was to identify physiological traits contributing to yield losses or yield stability under ozone stress in 18 contrasting wheat cultivars that had been pre-selected from a larger wheat population with known ozone tolerance. Plants were exposed to season-long ozone fumigation in open-top chambers at an average ozone concentration of 70 ppb with three additional acute ozone episodes of around 150 ppb. Compared to control conditions, average yield loss was 18.7 percent, but large genotypic variation was observed ranging from 2.7 to 44.6 percent. Foliar chlorophyll content represented by normalized difference vegetation index and net CO2 assimilation rate of young leaves during grain filling were the physiological traits most strongly correlated with grain yield losses or stability. Accumulative effects of chronic ozone exposure on photosynthesis were more detrimental for grain yield than instantaneous effects of acute ozone shocks, or accelerated senescence of older leaves represented by changes in the ratio of brown leaf area/green leaf area index. We used experimental data of two selected tolerant or sensitive varieties, respectively, to parametrize the LINTULCC2 crop model expanded with an ozone response routine. By specifying parameters representing the distinct physiological responses of contrasting genotypes, we simulated yield losses of 7 percent (tolerant) or 33 percent (sensitive). By considering genotypic differences in ozone response models, this study helps to improve the accuracy of simulation studies, estimate the effects of adaptive breeding, and identify physiological traits for the breeding of ozone tolerant wheat varieties that could deliver stable yields despite ozone exposure.

Chronic tropospheric ozone exposure reduces seed yield and quality in spring and winter oilseed rape

Oilseed rape (Brassica napus L.) is cultivated worldwide, producing 11.5% of global oilseeds at an economic value of 38 billion USD in 2020. It is sensitive to phytotoxic damage from exposure to tropospheric ozone (O3), a major air pollutant, which disrupts plant physiological processes and thus decreases biomass accumulation. As background ozone concentrations continue to increase globally, we investigated the impact of ozone exposure on seed and oil yield of a shorter-lived spring (cv. Click) and a longer-lived winter (cv. Phoenix) oilseed rape cultivar to ozone levels (treatments with peaks of 30, 55, 80, 110 ppbv) representative of typical European conditions where these cultivars are common. Thousand Seed Weight (TSW), an important measure of final yield, decreased more in Phoenix (40%) than Click (20%) with increasing ozone exposure. Click produced more racemes and many small seeds while Phoenix produced fewer racemes and larger seeds. However, seed quality declined more substantially in Click than Phoenix. The oil content in Click's seed significantly decreased with increased ozone exposure, while less desirable components (moisture, chlorophyll, ash) increased. Scaled to field-level, our findings imply substantial economic penalties for growers, with potential losses of 175–325 USD ha−1 in Click and 500–665 USD ha−1 in Phoenix under ozone concentrations typical of spring and summer periods in Europe. Decreased total yield would likely outweigh the benefits of any improvement in animal oilseed cake quality (increased protein and key micronutrients for livestock feed). Neither cultivar sustained visible injury at earlier growth stages, and Phoenix sustained photosynthesis even under high exposure, thereby making ozone an invisible threat. Our findings of reduced oilseed quantity and quality threaten oilseed rape production, but differences between the cultivars may also offer an opportunity for breeders and agronomists to identify and exploit variation in ozone tolerance in oilseed rape.

Altered lipidomic profiles in lung and serum of rat after sub-chronic exposure to ozone

Ozone (O) exposure not only causes lung injury and lung inflammation but also changes blood composition. Previous studies have mainly focused on inflammatory processes and metabolic diseases caused by acute or chronic ozone exposure. However, the effect of ozone on lipid expression profiles remains unclear. This study aimed to investigate the lipidomic changes in lung tissue and serum of rats after ozone exposure for three months and explore the lipid metabolic pathway involved in an ozone-induced injury. Based on the non-targeted lipidomic analysis platform of the UPLC Orbitrap mass spectrometry system, we found that sub-chronic exposure to ozone significantly changed the characteristics of lipid metabolism in lungs and serum of rats. First, the variation in sphingomyelin (SM) and triglyceride (TG) levels in the lung and serum after O3 exposure are shown. SM decreased in both tissues, while TG decreased in the lungs and increased in the serum. Further, the effect of ozone on glycerophospholipids in the lung and serum was completely different. Phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI) were the major glycerophospholipids whose levels were altered in the lung, while phosphatidylglycerol (PG), phosphatidic acid (PA), and phosphatidylcholine (PC) levels changed dramatically in the serum. Third, after O3 exposure, the level of monogalactosyldiacylglycerol (MGDG), mainly MGDG (43, 11), a saccharolipid, declined significantly and uniquely in the serum. These results suggested that sub-chronic O3 exposure may play a role in the development of several diseases through perturbation of lipidomic profiles in the lungs and blood. In addition, changes in the lipids of the lung and blood may induce or exacerbate respiratory diseases.

The Effect of Increased Ozone Levels on the Stable Carbon and Nitrogen Isotopic Signature of Wheat Cultivars and Landraces

Several studies have highlighted the negative effects of ozone (O3) on wheat development and productivity. The negative effects of O3 are mediated by changes in photosynthetic carbon and nitrogen metabolism, which are difficult and time-consuming to assess and are thus only measured sporadically throughout the plant cycle. Stable isotope measurements in grains can help integrate the effects of chronic O3 exposure over the lifespan of the plant. This particular study focuses on the extent to which the stomatal conductance and productivity of Mediterranean wheat are related to carbon and nitrogen isotopic signatures under chronic O3 exposure. An open top chamber experiment was designed to analyse the effects of the pollutant on 12 Spanish wheat genotypes, which included modern cultivars, old cultivars and landraces. Four O3 treatments were considered. Stomatal conductance (gs) measurements were carried out during anthesis, and yield and nitrogen content parameters were taken at maturity, along with the carbon (δ13C) and nitrogen (δ15N) isotopic composition measured in grains. Modern and old cultivars responded similarly to O3 and were sensitive to the pollutant regarding yield parameters and gs, while landraces were more O3-tolerant. Grain δ13C had a strong negative correlation with grain yield and stomatal conductance across genotypes and O3 conditions, and increased under higher O3 concentrations, showing its capacity to integrate O3 stress throughout the wheat cycle. Meanwhile, a higher nitrogen concentration in grains, coupled with smaller grains, led to an overall decreased grain nitrogen yield under higher O3 concentrations. This nitrogen concentration effect within the grain differed among genotypes bred at different ages, following their respective O3-sensitivity. δ15N showed a possible indirect effect of O3 on nitrogen redistribution, particularly under the highest O3 concentration. The correlations of δ15N and δ13C to the usual effects of ozone on the plant suggest their potential as indicators of chronic ozone exposure.

Ozone as eustress for enhancing secondary metabolites and bioactive properties in Salvia officinalis

Eliciting plants consists in the application of chemical, physical, and biological factors that induce stressful conditions, and so trigger defense mechanisms and the production of bioactive compounds and phytochemicals. In this study, the phenolic and volatile organic compound (VOCs) profiles of sage leaves under a chronic ozone (O3) exposure (120 ppb 5 h day−1 for 36 consecutive days) were investigated, elucidating also their antioxidant activity. The composition, yield, and antioxidant capacity of essential oils (EOs) obtained from sage leaves were also evaluated. Ozone exposure resulted in an overall increase of phenolic compounds. In terms of VOCs, O3 mainly reduced monoterpene emissions, while increased the production of sesquiterpenes (in both leaves and EOs). These O3-induced accumulations were triggered during the first weeks of exposure, whereas they disappeared at the last time of analysis, suggesting that sage plants lost their ability (or interest) in activating secondary metabolism under high doses of O3. The antioxidant capacity of all tested extracts resulted increased by O3 exposure. These outcomes support our speculation that the application of O3 for a limited period (i.e., a maximum of four weeks, at the investigated concentration) may become an effective biotechnological tool to improve the quality of sage leaf extracts.

Impact of chronic elevated ozone exposure on photosynthetic traits and anti-oxidative defense responses of Leucaena leucocephala (Lam.) de wit tree under field conditions

In this study, the impact of long term exposure of elevated ozone (+20 ppb above ambient) on photosynthetic traits and anti-oxidative defense system of Leucaena leucocephala, a tree of great economic importance, was studied in a Free Air Ozone Concentration Enrichment (O3-FACE) facility at different time intervals (6, 12, 18, and 24 months). Results showed that net photosynthesis, photosynthetic pigments and lipid peroxidation were significantly reduced after 6, 12 and 24 months of exposure to elevated ozone (eO3) whereas stomatal conductance and transpiration rate were significantly decreased after 12 months of exposure to eO3. Antioxidant enzymatic activities (catalase, ascorbate peroxidase and glutathione reductase) were significantly increased after 12 months of exposure to eO3. Ascorbate was increased significantly after 6 and 12 months of exposure to eO3 while reduced glutathione content declined significantly after 6 and 24 months of exposure to eO3. The study showed that there were several negative long lasting physiological and biochemical responses in Leucaena. The results provide evidence that Leucaena exhibited greater sensitivity to O3 during initial exposure (up to 12 months) but showed moderate tolerance by the end of the 2nd year.

Assessing the effects of elevated ozone on physiology, growth, yield and quality of soybean in the past 40 years: A meta-analysis

Soybean (Glycine max) production is seriously threatened by ground-level ozone (O3) pollution. The goal of our study is to summarize the impacts of O3 on physiology, growth, yield, and quality of soybean, as well as root parameters. We performed meta-analysis on the collated 48 peer-reviewed papers published between 1980 and 2019 to quantitatively summarize the response of soybean to elevated O3 concentrations ([O3]). Relative to charcoal-filtered air (CF), elevated [O3] significantly accelerated chlorophyll degradation, enhanced foliar injury, and inhibited growth of soybean, evidenced by great reductions in leaf area (−20.8%), biomass of leaves (−13.8%), shoot (−22.8%), and root (−16.9%). Shoot of soybean was more sensitive to O3 than root in case of biomass. Chronic ozone exposure of about 75.5 ppb posed pronounced decrease in seed yield of soybean (−28.3%). In addition, root environment in pot contributes to higher reduction in shoot biomass and yield of soybean. Negative linear relationships were observed between yield loss and intensity of O3 treatment, AOT40. The larger loss in seed yield was significantly associated with higher reduction in shoot biomass and other yield component. This meta-analysis demonstrates the effects of elevated O3 on soybean were pronounced, suggesting that O3 pollution is still a soaring threat to the productivity of soybean in regions with high ozone levels.

Hyperspectral Reflectance of Light-Adapted Leaves Can Predict Both Dark- and Light-Adapted Chl Fluorescence Parameters, and the Effects of Chronic Ozone Exposure on Date Palm (Phoenix dactylifera).

High-throughput and large-scale measurements of chlorophyll a fluorescence (ChlF) are of great interest to investigate the photosynthetic performance of plants in the field. Here, we tested the capability to rapidly, precisely, and simultaneously estimate the number of pulse-amplitude-modulation ChlF parameters commonly calculated from both dark- and light-adapted leaves (an operation which usually takes tens of minutes) from the reflectance of hyperspectral data collected on light-adapted leaves of date palm seedlings chronically exposed in a FACE facility to three ozone (O3) concentrations (ambient air, AA; target 1.5 × AA O3, named as moderate O3, MO; target 2 × AA O3, named as elevated O3, EO) for 75 consecutive days. Leaf spectral measurements were paired with reference measurements of ChlF, and predictive spectral models were constructed using partial least squares regression. Most of the ChlF parameters were well predicted by spectroscopic models (average model goodness-of-fit for validation, R2: 0.53–0.82). Furthermore, comparing the full-range spectral profiles (i.e., 400–2400 nm), it was possible to distinguish with high accuracy (81% of success) plants exposed to the different O3 concentrations, especially those exposed to EO from those exposed to MO and AA. This was possible even in the absence of visible foliar injury and using a moderately O3-susceptible species like the date palm. The latter view is confirmed by the few variations of the ChlF parameters, that occurred only under EO. The results of the current study could be applied in several scientific fields, such as precision agriculture and plant phenotyping.

Oxidative Stress in Ozone-Induced Chronic Lung Inflammation and Emphysema: A Facet of Chronic Obstructive Pulmonary Disease.

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke and characterized by chronic inflammation, alveolar destruction (emphysema) and bronchiolar obstruction. Ozone is a gaseous constituent of urban air pollution resulting from photochemical interaction of air pollutants such as nitrogen oxide and organic compounds. While acute exposure to ozone induces airway hyperreactivity and neutrophilic inflammation, chronic ozone exposure in mice causes activation of oxidative pathways resulting in cell death and a chronic bronchial inflammation with emphysema, mimicking cigarette smoke-induced COPD. Therefore, the chronic exposure to ozone has become a model for studying COPD. We review recent data on mechanisms of ozone induced lung disease focusing on pathways causing chronic respiratory epithelial cell injury, cell death, alveolar destruction, and tissue remodeling associated with the development of chronic inflammation and AHR. The initial oxidant insult may result from direct effects on the integrity of membranes and organelles of exposed epithelial cells in the airways causing a stress response with the release of mitochondrial reactive oxygen species (ROS), DNA, and proteases. Mitochondrial ROS and mitochondrial DNA activate NLRP3 inflammasome and the DNA sensors cGAS and STING accelerating cell death pathways including caspases with inflammation enhancing alveolar septa destruction, remodeling, and fibrosis. Inhibitors of mitochondrial ROS, NLRP3 inflammasome, DNA sensor, cell death pathways, and IL-1 represent novel therapeutic targets for chronic airways diseases underlined by oxidative stress.

Role of Interleukin-10 in COPD in Tobacco Smokers with Chronic Ozone Exposure

Role of Interleukin-10 in COPD in Tobacco Smokers with Chronic Ozone Exposure

Ozone-Induced Aryl Hydrocarbon Receptor Activation Controls Lung Inflammation via Interleukin-22 Modulation.

Airborne ozone exposure causes severe lung injury and inflammation. The aryl hydrocarbon Receptor (AhR) (1), activated in pollutant-induced inflammation, is critical for cytokine production, especially IL-22 and IL-17A. The role of AhR in ozone-induced lung inflammation is unknown. We report here that chronic ozone exposure activates AhR with increased tryptophan and lipoxin A4 production in mice. AhR−/− mice show increased lung inflammation, airway hyperresponsiveness, and tissue remodeling with an increased recruitment of IL-17A and IL-22-expressing cells in comparison to control mice. IL-17A- and IL-22-neutralizing antibodies attenuate lung inflammation in AhR−/− and control mice. Enhanced lung inflammation and recruitment of ILC3, ILC2, and T cells were observed after T cell-specific AhR depletion using the AhRCD4cre-deficient mice. Together, the data demonstrate that ozone exposure activates AhR, which controls lung inflammation, airway hyperresponsiveness, and tissue remodeling via the reduction of IL-22 expression.