Intracellular and Extracellular Cytokines in A549 Cells and THP1 Cells Exposed to Cigarette Smoke

Hołownia, Adam; Wielgat, Przemysław; Rysiak, Edyta; Braszko, Jan J.

doi:10.1007/5584_2016_214

Cited by 15 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1). Although this seems counterintuitive, given the strong association between smoking and lung disease, it is consistent with other studies that have found that cigarette smoke extract is strongly inflammatory only in the human A549 adenocarcinoma cell line but not in primary lung epithelial cells (13,15,46). This data is also consistent with recent data from our laboratory showing a twofold increase in IL-8 production in primary SAEC exposed to dung biomass smoke (25).…”

Section: Discussionsupporting

confidence: 92%

Cigarette smoke dampens antiviral signaling in small airway epithelial cells by disrupting TLR3 cleavage

Duffney

McCarthy

Nogales

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Cigarette smokers and people exposed to second-hand smoke are at an increased risk for pulmonary viral infections, and yet the mechanism responsible for this heightened susceptibility is not understood. To understand the effect of cigarette smoke on susceptibility to viral infection, we used an air-liquid interface culture system and exposed primary human small airway epithelial cells (SAEC) to whole cigarette smoke, followed by treatment with the viral mimetic polyinosinic polycytidylic acid (poly I:C) or influenza A virus (IAV). We found that prior smoke exposure strongly inhibited production of proinflammatory (interleukin-6 and interleukin-8) and antiviral [interferon-γ-induced protein 10 (IP-10) and interferons] mediators in SAECs in response to poly I:C and IAV infection. Impaired antiviral responses corresponded to increased infection with IAV. This was associated with a decrease in phosphorylation of the key antiviral transcription factor interferon response factor 3 (IRF3). Here, we found that cigarette smoke exposure inhibited activation of Toll-like receptor 3 (TLR3) by impairing TLR3 cleavage, which was required for downstream phosphorylation of IRF3 and production of IP-10. These results identify a novel mechanism by which cigarette smoke exposure impairs antiviral responses in lung epithelial cells, which may contribute to increased susceptibility to respiratory infections.

show abstract

Section: Discussionsupporting

confidence: 92%

Cigarette smoke dampens antiviral signaling in small airway epithelial cells by disrupting TLR3 cleavage

Duffney

McCarthy

Nogales

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…A correlation analysis revealed that IL-2, IL-5, IL-10, MDC, insulin, leptin, ACTH, Necropsobacter , and Actinobacillus were associated within the same network. Previous work has identified IL-2, IL-5, IL-10, and MDC to be modulated by smoking [ 74 , 75 , 76 , 77 , 78 ]. Among them, IL-2 is the only cytokine that increased in the smoker group when compared to nonsmokers.…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoking Modulation of Saliva Microbial Composition and Cytokine Levels

Rodríguez-Rabassa

López

Rodríguez-Santiago

et al. 2018

IJERPH

View full text Add to dashboard Cite

Tobacco use has been implicated as an immunomodulator in the oral cavity and contributes to the development of oral cancer. In the present study, we investigated the effects of cigarette smoking on bacterial diversity and host responses compared to healthy nonsmoking controls. Saliva samples were collected from eighteen smokers and sixteen nonsmoking individuals by passive drool. The 16S rRNA gene was used to characterize the salivary microbiome by using the Illumina MiSeq platform. Cytokine and chemokine expression analyses were performed to evaluate the host response. Significant differences in cytokine and chemokine expression levels of MDC, IL-10, IL-5, IL-2, IL-4, IL-7, adrenocorticotropic hormone (ACTH), insulin, and leptin were observed between smokers and nonsmokers. Taxonomic analyses revealed differences between the two groups, and some bacterial genera associated with the smokers group had correlations with hormones and cytokines identified as statistically different between smokers and nonsmokers. These factors have been associated with inflammation and carcinogenesis in the oral cavity. The data obtained may aid in the identification of the interactions between the salivary microbiome, host inflammatory responses, and metabolism in smokers.

show abstract

“…Raw gene count matrix for bulk RNA-seq was downloaded from GEO (accession number GSE147507) (62). The data contained gene expression count matrix of two lung carcinoma cell lines A549 (63,64) and Calu3 (65,66…”

Section: Data Collectionmentioning

confidence: 99%

Network Analysis and Transcriptome Profiling Identify Autophagic and Mitochondrial Dysfunctions in SARS-CoV-2 Infection

Singh

Chen

Judy

et al. 2020

Preprint

View full text Add to dashboard Cite

Lack of effective treatment strategy and vaccine makes SARS-CoV-2 infection a big threat to mankind. Analyzing the host transcriptional changes in response to virus infection will help delineate the biological processes impacted by the virus and will potentially facilitate drug development. Using RNA seq datasets of virus infected lung cell lines A549 (infected with either SARS-CoV-2 or Influenza A virus (IAV)) and Calu3 (infected with either SARS-CoV-2 or MERS-CoV), we present a detailed analysis of genes expression changes in response to each of these viral infections. Upregulation of the antiviral interferon signaling was observed with all three viral infections. However, upregulation of the cytokine/inflammatory processes, downregulation of mitochondrial organization and respiration processes, and perturbation in the autophagic processes were specifically observed in SARS-CoV-2 infected cells, which were absent in IAV infected cells. Upregulation of the inflammatory processes was concordant with the gene expression signature of COVID-19 lungs and with inflammatory symptoms observed in severe cases of COVID-19 patients. Coexpression networks analysis also facilitated the identification of protein-protein interaction (PPI) subnetworks of genes in the inflammation and mitochondrial processes that were either coordinately up or downregulated in SARS-CoV-2 infected cells, respectively. Comparing the expression of marker genes of lung cell types from single cell RNA seq data with expression profile of A549 cells revealed that they likely represent the lung epithelial lineage cells. The cellular processes uniquely perturbed in infected cells that were identified in this analysis likely delineates lung epithelial cells response to the SARS-CoV-2 infection. PathogenicityAs obligate parasites, the viruses, while evading the host cell immune response, should encode enough proteins to ensure replication, and spread, by relying on the host cell's machinery. These processes require an intricate series of interaction between the virus and host (9). While many of the elicited responses are common across pathogens, each virus also creates a unique transcriptional profile (10). Functional distinctions across viruses may arise due to distinct processes utilized by a virus for cellular entry, or for host immune system evasion, or for replication and dissemination (11). Severity of illness for SARS-CoV-2 infections is likely impacted by both the direct cytotoxic effects of the virus, and the effectiveness of the complex host response (12,13). While the immune response is essential to resolving the infection, dysregulation of the immune system can result in immunopathogenesis (14,15). A dysregulated immune response is caused by rapid viral replication, cytokine storms delayed interferon response, and macrophage infiltration and excessive proinflammatory cytokines (14). This immunopathogenesis mechanism is supported by the observation of decreased viral loads occurring with increased disease severity (6). However, efforts to unders...

show abstract

Intracellular and Extracellular Cytokines in A549 Cells and THP1 Cells Exposed to Cigarette Smoke

Cited by 15 publications

References 22 publications

Cigarette smoke dampens antiviral signaling in small airway epithelial cells by disrupting TLR3 cleavage

Cigarette smoke dampens antiviral signaling in small airway epithelial cells by disrupting TLR3 cleavage

Cigarette Smoking Modulation of Saliva Microbial Composition and Cytokine Levels

Network Analysis and Transcriptome Profiling Identify Autophagic and Mitochondrial Dysfunctions in SARS-CoV-2 Infection

Contact Info

Product

Resources

About