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 μg/mL) of WS-CM and one high dose of STE (100 μg/mL) were similar to those from untreated controls. Cells treated with medium and high doses of WS-CM (1.0 and 3.0 μg/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 (IFNγ, TNFα, and IL-2), while CSF1-R and IL17RA were upregulated. Pre-treatment with high doses of WS-CM abolished agonist-stimulated secretion of IFNγ, TNF and IL-2 proteins. Pathway analyses revealed that higher doses of WS-CM inhibited NF-ĸB 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.
Highlights
Chronic cigarette smoking increases risk for the development of cardiovascular disease, stroke, chronic obstructive pulmonary disease (COPD) and cancer[1,2,3,4]
To gain an understanding of how exposure to tobacco products could impact the responsiveness of immune cells to external challenges, we examined gene expression profiles of tobacco product preparations (TPPs)-treated peripheral blood mononuclear cells (PBMCs) stimulated with immune activators
Whole Smoke-Conditioned Medium (WS-CM) pre-treated samples were clustered closer to each other than to the medium or high dose WS-CM pretreated samples (Fig. 1). These results show that while the treatments resulted in distinct gene expression profiles, the gene expression changes produced by Smokeless Tobacco Extracts (STE) and low dose WS-CM were more similar to control samples than to samples treated with medium or high dose WS-CM
Summary
Chronic cigarette smoking increases risk for the development of cardiovascular disease, stroke, chronic obstructive pulmonary disease (COPD) and cancer[1,2,3,4]. The oxidative stress-driven pro-inflammatory conditions induced by exposure to combustible tobacco preparations are suggested to be causal in dysregulated inflammation and immune signaling[14]. We and others have utilized PBMCs as an ex vivo model test system to assess how different tobacco products may alter the inflammatory status in consumers[14,15,16,17]. These studies have shown that combustible, but not non-combusted tobacco product preparations (TPPs) like smokeless tobacco, markedly suppress Toll Like Receptor (TLR) agonist-stimulated cytokine secretion and cytolytic functions of effector cells[14]. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) signaling pathway plays a key role in regulating inflammation and immune responses[18,19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
