Project description:Airway epithelial cells are the first cells of the lungs to be exposed to the toxic agents contained within cigarette smoke. Accordingly, the response of these cells to this challenge is of considerable interest in the context of diseases in which cigarette smoke is a major aetiological factor. We used Affymetrix microarrays to study the effects of repeated cigarette smoke challenge on three-dimensional human lung airway epithelial cultures.
Project description:Airway epithelial cells are the first cells of the lungs to be exposed to the toxic agents contained within cigarette smoke. Accordingly, the response of these cells to this challenge is of considerable interest in the context of diseases in which cigarette smoke is a major aetiological factor. We used Affymetrix microarrays to study the effects of repeated cigarette smoke challenge on three-dimensional human lung airway epithelial cultures. We have used cultures from four individual donors, and compared the effects of repeated cigarette smoke challenge (30mins exposure on four separate days), with no challenge.
Project description:To study the effect of cigarette smoke exposure on Sars-Cov2 infection, we directly exposed mucociliary air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term cigarette smoke and infected them with live SARS-CoV-2. We set out to examine the underlying mechanisms governing the increased susceptibility of cigarette smoke exposed ALI cultures to SARS-CoV-2 infection by usingle cell profiling of the cultures, which showed that interferon response genes were induced in SARS-CoV-2 infected airway epithelial cells in ALI cultures but smoking exposure together with SARS-CoV-2 infection reduced the interferon response.
Project description:To investigate the biochemical and genetic alterations that occur in response to cigarette smoke exposure among airway epithelial cells from different sites in the lungs, we performed microarray-based analysis using small airway epithelial cells (SAEC) and normal human bronchial epithelial cells (NHBE) following 24 h of cigarette smoke extract (CSE). In microarray-based analysis, the small airway showed higher susceptibility to CS compared to the large airway, such as enhanced expression of inflammatory-related pathways including the TNF signaling pathway. Among the TNF-related genes, PTGS2, also known as COX-2, showed the greatest difference in expression levels, with higher CSE-induced increments of both mRNA and protein expression in SAEC compared to NHBE.
Project description:To investigate the effect of cigarette smoke exposure on gene expression in airway epithelial cells of Canton S Drosophila melanogaster larvae, we isolated the airways of cigarette smoke exposed larvae and air controls. We then performed gene expression profiling analysis using data obtained from RNA-seq of smoke-exposed males, smoke-exposed females, air-control males and air-control females. For each group 4 biological replicates were prepared, representing 40-50 larval airways.
Project description:The biological impact of an aerosol of a potential modified-risk tobacco product, carbon heated tobacco product 1.2 (CHTP1.2), was comprehensively assessed for the first time in vitro using human small airway and nasal epithelial models following a systems toxicology approach. The potentially reduced effects of CHTP1.2 aerosol exposure were benchmarked against those of 3R4F cigarette smoke at similar nicotine concentrations. Experimental repetitions were conducted for which new batches of small airway and nasal cultures were exposed to CHTP1.2 aerosol or 3R4F smoke for 28 minutes. The biological impacts were determined based on a collection of endpoints including morphology, cytotoxicity, proinflammatory mediator profiles, cytochrome P450 1A1/1B1 activity, global mRNA and microRNA changes and proteome profiles. Alterations in mRNA expression were detected in cultures exposed to CHTP1.2 aerosol, without noticeable morphological changes and cytotoxicity, and minimal impact on proinflammatory mediator and proteome profiles. The changes linked to CHTP1.2 aerosol exposure, when observed, were transient. However, the impact of 3R4F smoke exposure persisted long post-exposure and greater than CHTP1.2 aerosol. Morphological changes were observed only in cultures exposed to 3R4F smoke. The lower biological effects of CHTP1.2 aerosol than 3R4F smoke exposure were observed similarly in both small airway and nasal epithelial cultures.
Project description:The biological impact of an aerosol of a potential modified-risk tobacco product, carbon heated tobacco product 1.2 (CHTP1.2), was comprehensively assessed for the first time in vitro using human small airway and nasal epithelial models following a systems toxicology approach. The potentially reduced effects of CHTP1.2 aerosol exposure were benchmarked against those of 3R4F cigarette smoke at similar nicotine concentrations. Experimental repetitions were conducted for which new batches of small airway and nasal cultures were exposed to CHTP1.2 aerosol or 3R4F smoke for 28 minutes. The biological impacts were determined based on a collection of endpoints including morphology, cytotoxicity, proinflammatory mediator profiles, cytochrome P450 1A1/1B1 activity, global mRNA and microRNA changes and proteome profiles. Alterations in mRNA expression were detected in cultures exposed to CHTP1.2 aerosol, without noticeable morphological changes and cytotoxicity, and minimal impact on proinflammatory mediator and proteome profiles. The changes linked to CHTP1.2 aerosol exposure, when observed, were transient. However, the impact of 3R4F smoke exposure persisted long post-exposure and greater than CHTP1.2 aerosol. Morphological changes were observed only in cultures exposed to 3R4F smoke. The lower biological effects of CHTP1.2 aerosol than 3R4F smoke exposure were observed similarly in both small airway and nasal epithelial cultures.
