Cigarette smoke preparations, not moist snuff, impair expression of genes involved in immune signaling and cytolytic functions.
Gang LiuSubhashini ArimilliEvan SavageGaddamanugu L PrasadPublished in: Scientific reports (2019)
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.
Keyphrases
- immune response
- poor prognosis
- dendritic cells
- rheumatoid arthritis
- high dose
- toll like receptor
- genome wide
- oxidative stress
- signaling pathway
- binding protein
- inflammatory response
- copy number
- gene expression
- induced apoptosis
- cell death
- single cell
- dna methylation
- combination therapy
- high glucose
- systemic lupus erythematosus
- smoking cessation
- systemic sclerosis
- interstitial lung disease