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Cigarette smoke preparations, not moist snuff, impair expression of genes involved in immune signaling and cytolytic functions.

ABSTRACT: Cigarette smoke-induced chronic inflammation is associated with compromised immune responses. To understand how tobacco products impact immune responses, we assessed transcriptomic profiles in peripheral blood mononuclear cells (PBMCs) pretreated with Whole Smoke-Conditioned Medium (WS-CM) or Smokeless Tobacco Extracts (STE), and stimulated with lipopolysaccharide, phorbol myristate and ionomycin (agonists). Gene expression profiles from PBMCs treated with low equi-nicotine units (0.3??g/mL) of WS-CM and one high dose of STE (100??g/mL) were similar to those from untreated controls. Cells treated with medium and high doses of WS-CM (1.0 and 3.0??g/mL) exhibited significantly different gene expression profiles compared to the low WS-CM dose and STE. Pre-treatment with higher doses of WS-CM inhibited the expression of several pro-inflammatory genes (IFN?, TNF?, and IL-2), while CSF1-R and IL17RA were upregulated. Pre-treatment with high doses of WS-CM abolished agonist-stimulated secretion of IFN?, TNF and IL-2 proteins. Pathway analyses revealed that higher doses of WS-CM inhibited NF-?B signaling, immune cell differentiation and inflammatory responses, and increased apoptotic pathways. Our results show that pre-treatment of PBMCs with higher doses of WS-CM inhibits immune activation and effector cytokine expression and secretion, resulting in a reduced immune response, whereas STE exerted minimal effects.

SUBMITTER: Liu G

PROVIDER: S-EPMC6746724 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Cigarette smoke preparations, not moist snuff, impair expression of genes involved in immune signaling and cytolytic functions.

Liu Gang G Arimilli Subhashini S Savage Evan E Prasad G L GL

Scientific reports 20190916 1

Cigarette smoke-induced chronic inflammation is associated with compromised immune responses. To understand how tobacco products impact immune responses, we assessed transcriptomic profiles in peripheral blood mononuclear cells (PBMCs) pretreated with Whole Smoke-Conditioned Medium (WS-CM) or Smokeless Tobacco Extracts (STE), and stimulated with lipopolysaccharide, phorbol myristate and ionomycin (agonists). Gene expression profiles from PBMCs treated with low equi-nicotine units (0.3 μg/mL) of ...[more]

PMID: 31527707

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Project description:Cigarette smoking exerts diverse physiological effects including immune suppression. Existing US epidemiological data show that consumption of smokeless tobacco products, such as moist snuff, is less harmful relative to cigarette smoking. In efforts to understand the molecular changes due to consumption of different tobacco product classes, we have shown recently that smokers exhibit distinct peripheral blood mononuclear cells (PBMCs) gene expression patterns relative to moist snuff users and non-tobacco consumers (NTCs). To better characterize the biological effects exerted from the use of different tobacco products, a genome-wide gene expression study, using a cultured PBMC model, was performed. Gene expression profiles from PBMCs treated with low equi-nicotine units (0.3 µg/ml) of WS-CM and a single high dose of STE (100 µg/ml) were similar to those from untreated controls. Cells treated with medium and high equi-nicotine unit doses of WS-CM (1.0 and 3.0 µg/ml) exhibited significantly different gene expression profiles compared to the low equi-nicotine WS-CM dose and STE. Pre-treatment with higher doses of WS-CM inhibited the expression of several pro-inflammatory genes that regulate immune responses, including IFNγ, TNFα, and IL-2. Gene expression changes of these genes and other cytokine signaling genes were confirmed by qRT-PCR. Moreover, secretion of IFNγ, TNFα and IL-2 proteins was abolished by WS-CM pre-treatment even after 24 hours of toll like receptor stimulation. Additionally, pathway analyses revealed that higher doses of WS-CM inhibited NF-ĸβ signaling and a wide range of signaling pathways associated with immune cell differentiation and inflammatory responses, and increased expression of genes involved in apoptosis. Collectively, our results show that pre-treatment of PBMCs with higher doses of WS-CM inhibits immune activation and effector cytokine expression and secretion, resulting in a reduced immune response, whereas STE had minimal effect.

Project description:IntroductionTobacco product characteristics convey product attributes to potential users. This study aimed to assess independent contributions of specific e-cigarette and smokeless tobacco product characteristics to adolescents' perceptions about these products.MethodsIn 2019-2020, students (N=1003) attending a convenience sample of 7 high schools in California (USA) were individually randomized to one of two discrete choice experiments, featuring either electronic cigarettes (e-cigarettes) or moist snuff. Participants were presented like-product pairs of randomlygenerated hypothetical tobacco products differing in device type, flavor, vapor cloud, and nicotine amount (for e-cigarettes) or differing in brand, flavor, cut, and price (for moist snuff). Within pairs, participants were asked about which product they were more curious, was more dangerous, would give a greater 'buzz,' and would be easier to use. Conditional logistic regression was used to quantify independent associations of product characteristics to participants' choices.ResultsEach e-cigarette and moist snuff characteristic was independently associated with multiple product perceptions. All non-tobacco flavors were associated with more curiosity and perceived ease-of-use but lower perceived danger. Tank and pod-type e-cigarettes were viewed as easier to use and garnered more curiosity than 'cigalike' or 'drip-mod' devices. Smaller vapor cloud e-cigarettes and lower-price moist snuff were viewed as less dangerous, less buzz-inducing, and easier to use. Product ever users held stronger perceptions than never users about device type (e-cigarettes) and brands (moist snuff), while product naïve participants more strongly associated flavor with danger and buzz.ConclusionsTobacco product characteristics convey product attributes to adolescents that may increase appeal. Restricting specific characteristics, including flavors, could reduce positive perceptions of these products among youth.

Project description:Use of smokeless tobacco products (STPs) is associated with oral cavity cancer and other health risks. Comprehensive analysis for chemical composition and toxicity is needed to compare conventional and newer STPs with lower tobacco-specific nitrosamines (TSNAs) yields. Seven conventional and 12 low-TSNA moist snuff products purchased in the U.S., Sweden, and South Africa were analyzed for 18 chemical constituents (International Agency for Research on Cancer classified carcinogens), pH, nicotine, and free nicotine. Chemicals were compared in each product using Wilcoxon rank-sum test and principle component analysis (PCA). Conventional compared to low-TSNA moist snuff products had higher ammonia, benzo[a]pyrene, cadmium, nickel, nicotine, nitrate, and TSNAs and had lower arsenic in dry weight content and per mg nicotine. Lead and chromium were significantly higher in low-TSNA moist snuff products. PCA showed a clear difference for constituents between conventional and low-TSNA moist snuff products. Differences among products were reduced when considered on a per mg nicotine basis. As one way to contextualize differences in constituent levels, probabilistic lifetime cancer risk was estimated for chemicals included in The University of California's carcinogenic potency database (CPDB). Estimated probabilistic cancer risks were 3.77-fold or 3-fold higher in conventional compared to low-TSNA moist snuff products under dry weight or under per mg nicotine content, respectively. In vitro testing for the STPs indicated low level toxicity and no substantial differences. The comprehensive chemical characterization of both conventional and low-TSNA moist snuff products from this study provides a broader assessment of understanding differences in carcinogenic potential of the products. In addition, the high levels and probabilistic cancer risk estimates for certain chemical constituents of smokeless tobacco products will further inform regulatory decision makers and aid them in their efforts to reduce carcinogen exposure in smokeless tobacco products.

Project description:BackgroundSmokeless tobacco (ST) products are widely used throughout the world and contribute to morbidity and mortality in users through an increased risk of cancers and oral diseases. Bacterial populations in ST contribute to taste, but their presence can also create carcinogenic, Tobacco-Specific N-nitrosamines (TSNAs). Previous studies of microbial communities in tobacco products lacked chemistry data (e.g. nicotine, TSNAs) to characterize the products and identify associations between carcinogen levels and taxonomic groups. This study uses statistical analysis to identify potential associations between microbial and chemical constituents in moist snuff products.MethodsWe quantitatively analyzed 38 smokeless tobacco products for TSNAs using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and nicotine using gas chromatography with mass spectrometry (GC-MS). Moisture content determinations (by weight loss on drying), and pH measurements were also performed. We used 16S rRNA gene sequencing to characterize the microbial composition, and additionally measured total 16S bacterial counts using a quantitative PCR assay.ResultsOur findings link chemical constituents to their associated bacterial populations. We found core taxonomic groups often varied between manufacturers. When manufacturer and flavor were controlled for as confounding variables, the genus Lactobacillus was found to be positively associated with TSNAs. while the genera Enteractinococcus and Brevibacterium were negatively associated. Three genera (Corynebacterium, Brachybacterium, and Xanthomonas) were found to be negatively associated with nicotine concentrations. Associations were also investigated separately for products from each manufacturer. Products from one manufacturer had a positive association between TSNAs and bacteria in the genus Marinilactibacillus. Additionally, we found that TSNA levels in many products were lower compared with previously published chemical surveys. Finally, we observed consistent results when either relative or absolute abundance data were analyzed, while results from analyses of log-ratio-transformed abundances were divergent.

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Cigarette smoke preparations, not moist snuff, impair expression of genes involved in immune signaling and cytolytic functions.

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Cigarette smoke preparations, not moist snuff, impair expression of genes involved in immune signaling and cytolytic functions.

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