Cigarette Smoke Extract Induces Cytotoxicity on Human Nasal Epithelial Cells

Lan, Ming‐Ying; Ho, Ching‐Yin; Lee, Te‐Chang; Yang, An-Hang

doi:10.2500/ajr.2007.21.2966

Cited by 26 publications

(29 citation statements)

References 16 publications

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“…The concentrations of CSE used can range from 100% CSE for 15 minutes [28] to a 1% CSE for 24 hours (in those studies which use a single cigarette to prepare the initial “100%” stock CSE) [29]. A study exposing primary human nasal epithelial cells to CSE for 1 h, 2 h, and 4 h reported a time and dose-dependent cytotoxicity of CSE [30].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Nasal and Bronchial Epithelial Cells Obtained from Patients with COPD

2012

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For in vitro studies of airway pathophysiology, primary epithelial cells have many advantages over immortalised cell lines. Nasal epithelial cells are easier to obtain than bronchial epithelial cells and can be used as an alternative for in vitro studies. Our objective was to compare nasal and bronchial epithelial cells from subjects with COPD to establish if these cells respond similarly to pro-inflammatory stimuli. Cell cultures from paired nasal and bronchial brushings (21 subjects) were incubated with cigarette smoke extract (CSE) prior to stimulation with Pseudomonas aeruginosa lipopolysaccharide. IL-6 and IL-8 were measured by ELISA and Toll-like receptor 4 (TLR-4) message and expression by RT-PCR and FACS respectively. IL-8 release correlated significantly between the two cell types. IL-6 secretion was significantly less from bronchial compared to nasal epithelial cells and secreted concentrations did not correlate. A 4 h CSE incubation was immunosuppressive for both nasal and bronchial cells, however prolonged incubation for 24 h was pro-inflammatory solely for the nasal cells. CSE reduced TLR-4 expression in bronchial cells only after 24 h, and was without effect on mRNA expression. In subjects with COPD, nasal epithelial cells cannot substitute for in vitro bronchial epithelial cells in airway inflammation studies.

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Section: Discussionmentioning

confidence: 99%

Comparison of Nasal and Bronchial Epithelial Cells Obtained from Patients with COPD

2012

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“…Concentrations of CSE used can range from 100% CSE for 15 min [17] to 1% CSE for 24 h (in those studies which use a single cigarette to prepare the initial ''100%'' stock CSE) [27]. Other investigators have prepared CSE using multiple cigarettes ranging from two cigarettes up to as many as five [13,28]. Many of these studies assessed soluble mediator release and a single time point, but two studies highlight that caution is required as CSE can delay LPS-induced release of IL-8 and granulocyte-macrophage colony stimulating factor in primary epithelial cells, but yet it was not abolished completely at later time points [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…Activated NF-kB can have pro-apoptotic effects in certain cells, yet be protective of apoptosis in others [11]. CSE has been reported to induce apoptosis in PBECs [12] and primary nasal epithelial cells by some [13], but not by other investigators [10]. Furthermore, recent research using PBECs indicated that CSE induces necrosis rather than apoptosis [14].…”

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confidence: 99%

Airway epithelial cell apoptosis and inflammation in COPD, smokers and nonsmokers

et al. 2012

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We hypothesised that primary bronchial epithelial cells (PBECs) from subjects with chronic obstructive pulmonary disease (COPD) respond differently to Pseudomonas aeruginosa lipopolysaccharide (LPS) after cigarette smoke extract (CSE) exposure than PBECs obtained from smokers without airflow obstruction and nonsmokers.PBECs from 16 COPD subjects, 10 smokers without airflow obstruction and nine nonsmokers were cultured at air-liquid interface. Cultures were incubated with CSE prior to stimulation with P. aeruginosa LPS. Interleukin (IL)-6 and IL-8 were measured by ELISA and Toll-like receptor (TLR)-4 expression by fluorescence-activated cell sorter. Activation of nuclear factor (NF)-kB was determined by Western blotting and ELISA, and MAPK and caspase-3 activity by Western blotting. Apoptosis was evaluated using Annexin-V staining and the terminal transferase-mediated dUTP nick end-labelling methods.Constitutive release of IL-8 and IL-6 was greatest from the COPD cultures. However, CSE pretreatment followed by P. aeruginosa LPS stimulation reduced IL-8 release from COPD PBECs, but increased it from cells of smokers without airflow obstruction and nonsmokers. TLR-4 expression, MAPK and NF-kB activation in COPD cultures were reduced after CSE treatment, but not in the smokers without airflow obstruction or nonsmoker groups, which was associated with increased apoptosis.CSE attenuates inflammatory responses to LPS in cells from people with COPD but not those from nonsmoking individuals and those who smoke without airflow obstruction.

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“…Exposure to CS is associated with nasal inflammation (Lee and Kim, 2013;Lan et al, 2007;Huvenne et al, 2010). A possible role of CS exposure in sinonasal cancer has also been discussed ('t Mannetje et al, 1999;Kuper et al, 2002;Sham et al, 2010;Moon et al, 2010;d'Errico et al, 2013).…”

Section: R4f Smoke and Ths22 Aerosol Exposure And Endpoint Generationmentioning

confidence: 99%

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

Iskandar

Mathis

Martin

et al. 2017

ALTEX

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ratory animals -to reduce the number of animals, to refine the design of procedures such that pain and distress are minimized, and to replace animal models with alternative methods and lower organisms when possible (Doke and Dhawale, 2015). In this regard, the capability to preserve human respiratory cells in culture provides a tool not only to generate mechanistic data, but also to improve the predicted effects of exposure hazard through inhalation in humans. An emphasis on assessment studies using human-derived in vitro culture systems will reduce the problems that are inherent to interspecies translatability (Manuppello and Sullivan, 2015).In vitro toxicology approaches have evolved from focusing on the molecular changes within a cell to understanding the toxicity-related mechanisms (cell-cell interactions) in models IntroductionMechanistic investigation of the impact of exposure on the lower airway remains challenging because access to lung tissues is limited. Although biopsy samples can be obtained from patients/donors for mechanistic studies of exposure-induced injury, a biopsy procedure is invasive and there are related ethical concerns (Peppercorn, 2013). Alternatively, animal studies allow the collection of biological samples from various animal models of human diseases. However, biological responses can vary among animal species, and findings obtained from animal studies may not apply to humans. Alternatives to animal testing have been proposed to overcome these drawbacks, including the 3Rs strategy -reduction, refinement, and replacement of labo- Research SummaryIn vitro toxicology approaches have evolved from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus, the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. Aligned with 3Rs strategy, this study aimed to explore the relevance of a human 3-D nasal culture model to assess the toxicological impact of aerosols generated from a candidate modified risk tobacco product (cMRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F. A series of experimental repetitions, where multiple concentrations of THS2.2 aerosol and 3R4F smoke were applied, were conducted to obtain reproducible measurements to understand the cellular/molecular changes that occur following exposure. In agreement with "Toxicity Testing in the 21 st Century -a Vision and a Strategy", this study implemented a systems toxicology approach and found that for all tested concentrations the impa...

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Cigarette Smoke Extract Induces Cytotoxicity on Human Nasal Epithelial Cells

Abstract: CSE induces cytotoxicity on primary human nasal epithelial cells and the morphological findings closely mimic partition apoptosis.

Cited by 26 publications

References 16 publications

Comparison of Nasal and Bronchial Epithelial Cells Obtained from Patients with COPD

Comparison of Nasal and Bronchial Epithelial Cells Obtained from Patients with COPD

Airway epithelial cell apoptosis and inflammation in COPD, smokers and nonsmokers

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

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