Inflammatory and Repair Pathways Induced in Human Bronchoalveolar Lavage Cells with Ozone Inhalation

Leroy, Pascale; Tham, Andrea; Wong, Hofer; Tenney, Rachel; Chen, Chun; Stiner, Rachel; Balmes, John R.; Paquet, Agnès; Arjomandi, Mehrdad

doi:10.1371/journal.pone.0127283

Cited by 29 publications

(20 citation statements)

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“…A useful model to explore this effect is the use of O 3 to stimulate the bronchial epithelium prior to examination of the cellular functions of adjacent fibroblasts not in direct contact of O 3 ( 29 ). O 3 is a common major component of air pollution and has been revealed in various studies to cause airway epithelial shedding, airway inflammation and airway hyperresponsiveness ( 16 , 30 ). Therefore, the aim of the present study was to co-culture HLFs with airway epithelial cells pre-stimulated with O 3 and subsequently measure the functional changes, including collagen synthesis, of the fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

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Effects of ozone stimulation of bronchial epithelial cells on proliferation and collagen synthesis of co‑cultured lung fibroblasts

et al. 2018

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Ozone (O3) as a major air pollutant is widely recognized for causing pathological changes of the airway system. However, it is not clear whether O3 exposure of bronchial epithelial cells (BECs) influences the proliferation and collagen synthesis of submucosal fibroblasts and contributes to the pathogenesis of airway remodeling in diseases, including asthma. In the present study, a co-culture method was applied to culture human lung fibroblasts (HLFs) with human bronchial epithelial cells (HBECs) that were pre-stimulated with O3. Following co-culture for up to 24 h, the proliferation of HLFs was measured using MTT colorimetry. Furthermore, the collagen synthesis capacity of HLFs was determined by the level of hydroxyproline. In addition, the protein expression levels of cytokines, including transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2) were assessed. Results indicated that the proliferation of HLFs co-cultured with HBECs was significantly inhibited when compared with HLFs cultured alone (P<0.05). By contrast, co-culture with O3-stimulated HBECs significantly promoted the proliferation of HLFs compared with the HLFs cultured alone or those cultured with HBECs but no O3 stimulation, respectively (P<0.05 and P<0.01). Furthermore, similar effects were observed regarding the collagen synthesis capacity of HLFs co-cultured with HBECs for 24. In the supernatant, TGF-β1 concentration was continuously increased over 24 h, whereas the concentration of PGE2 increased and plateaued between 12 to 24 h and TNF-α concentration was not significantly altered during the assessed time period. To conclude, the present results suggest that O3 pre-exposure of HBECs may promote the transformation of HLFs from the typical inhibitory state into a promoting state with respect to proliferation and collagen synthesis, which may likely occur through a mechanism that influences the balance between pro- and anti-inflammatory factors, including TGF-β1 and PGE2. The present findings may improve the understanding of the mechanism involved in O3-induced airway remodeling from a novel perspective of maintenance/loss of steady-state function of the airway epithelium.

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Section: Discussionmentioning

confidence: 99%

“…Notably, there is little evidence to support whether O 3 exposure may result in airway remodeling. The limited reports regarding this may partly be due to the fact that O 3 directly targets bronchial epithelial cells (BECs) but not the fibroblasts that reside beneath these cells, which serve a key role in airway remodeling ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of ozone stimulation of bronchial epithelial cells on proliferation and collagen synthesis of co‑cultured lung fibroblasts

et al. 2018

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“…In the case of examining toxicant-induced responses, genomic profiling studies are useful for identifying markers of exposure and early effect and comprehensively describing a toxicant's effects at the transcriptional level. Previous studies that investigated transcriptional responses in whole lung tissue and in inflammatory cells recruited to the lungs following O3 exposure have broadened our appreciation of O3-response pathways and mechanisms of toxicity, including the involvement of heat-shock proteins (Hspa1), extracellular matrix remodeling enzymes (Mmp2, Mmp9), and various proinflammatory signaling pathways (Tnfr family members, Rela), amongst others (GOHIL et al 2003;NADADUR et al 2005;KOOTER et al 2007;BACKUS et al 2010;BAUER et al 2011;GABEHART et al 2014;LEROY et al 2015;VERHEIN 2015;WARD 2015;CIENCEWICKI et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional profiling of the murine airway response to acute ozone exposure

Tovar

Smith

Thomas

et al. 2019

Preprint

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Exposure to ambient ozone (O3) pollution causes airway inflammation, epithelial injury, and decreased lung function. Long-term exposure is associated with increased mortality and exacerbations of respiratory conditions. While the adverse health effects of O3 exposure have been thoroughly described, less is known about the molecular processes that drive these outcomes. The aim of this study was to describe the cellular and molecular alterations observed in murine airways after exposure to either 1 or 2 ppm O3. After exposing adult, female C57BL/6J mice to filtered air, 1 or 2 ppm O3 for 3 hours, we assessed hallmark responses including airway inflammatory cell counts, epithelial permeability, cytokine secretion, and morphological alterations of the large airways. Further, we performed RNA-seq to profile gene expression in two critical tissues involved in O3 responses: conducting airways (CA) and airway macrophages (AM). We observed a concentration-dependent increase in airway inflammation and injury, and a large number of genes were differentially expressed in both target tissues at both concentrations of O3. Genes that were differentially expressed in CA were generally associated with barrier function, detoxification processes, and cellular proliferation. The differentially expressed genes in AM were associated with innate immune signaling, cytokine production, and extracellular matrix remodeling. Overall, our study has described transcriptional responses to acute O3 exposure, revealing both shared and unique gene expression patterns across multiple concentrations of O3 and in two important O3-responsive tissues. These profiles provide broad mechanistic insight into pulmonary O3 toxicity, and reveal a variety of targets for refined followup studies.

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“…Известно, что неорганическая пыль [26] и токсичные газы [27] инициируют оксидативный стресс. В настоящем исследовании также определена высокая активность процессов перекисного окисления, ассоциация тяжести оксидативного стресса со стажем работы и дозой промышленного аэрозоля.…”

Section: таблица 3 влияние производственного этиологического фактора unclassified

Peculiarities of Cellular Molecular Mechanisms of Professional Chronic Obstructive Pulmonary Disease

Шпагина¹,

Kotova²,

Сараскина³

et al. 2018

SMR

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Цель исследования. Изучение механизмов воспаления при профессиональной хронической обструктивной болезни легких (ХОБЛ) в условиях воздействия токсичных газов или неорганической пыли. Материал и методы. Дизайн-одноцентровое проспективное когортное наблюдательное исследование больных профессиональной ХОБЛ от действия токсичных газов (n=55) и неорганической пыли (n=101). Группа сравнения-больные ХОБЛ курильщики табака (n=103), контрольная-условно здоровые лица (n=99). Диагноз ХОБЛ-критерии GOLD 2011-2017. Определяли концентрации в системной циркуляции провоспалительных цитокинов, факторов роста, молекул систем протеиназы-антипротеиназы, оксиданты-антиоксиданты, эндотелиальных факторов, Д-димеров методом твердофазного иммуноферментного анализа. Влияние производственного фактора на клеточный состав лаважной жидкости и сывороточные концентрации молекул биомеханизма развития ХОБЛ устанавливали методом ковариационного дисперсионного анализа. Результаты. При ХОБЛ от действия токсичных газов преобладал эозинофильный тип воспаления (у 58 % больных), от действия пыли-пауцигранулоцитарный (у 70 % больных). Молекулярный паттерн воспаления при ХОБЛ от действия токсичных газов отличался повышением в системной циркуляции концентраций IL1β, MIF, TGFβ1, ММР1 и ММР9, снижением VEGF A и оксида азота, при ХОБЛ от действия неорганической пыли-повышением FGF2 и 8-изо-PGF2α. Во множественной регрессионной модели при ХОБЛ от действия токсичных газов ОФВ1 ассоциирован с МСР1 и TGFβ1, от действия пыли-с IL1β. Выявленные различия позволяют говорить о влиянии производственного этиологического фактора на фенотип ХОБЛ за счет модификации эндотипа. Определены маркеры ХОБЛ от действия токсичных газов-сочетание сывороточных концентраций IL1β (В=0,027), TGFβ1 (В=0,00009), VEGF А (В=-0,0003) и неорганической пыли-IL1β (В = 0,017), FGF2 (В=0,045). Заключение. Производственный фактор влияет на особенности биомеханизма развития профессиональной ХОБЛ.

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Inflammatory and Repair Pathways Induced in Human Bronchoalveolar Lavage Cells with Ozone Inhalation

Cited by 29 publications

References 50 publications

Effects of ozone stimulation of bronchial epithelial cells on proliferation and collagen synthesis of co‑cultured lung fibroblasts

Effects of ozone stimulation of bronchial epithelial cells on proliferation and collagen synthesis of co‑cultured lung fibroblasts

Transcriptional profiling of the murine airway response to acute ozone exposure

Peculiarities of Cellular Molecular Mechanisms of Professional Chronic Obstructive Pulmonary Disease

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