Tobacco smoke and nicotine suppress expression of activating signaling molecules in human dendritic cells

Abstract

Cigarette smoke has significant toxic effects on the immune system, and increases the risk of developing autoimmune diseases; one immunosuppressive effect of cigarette smoke is that it inhibits the T cell-stimulating, immunogenic properties of myeloid dendritic cells (DCs). As the functions of DCs are regulated by intra-cellular signaling pathways, we investigated the effects of cigarette smoke extract (CSE) and nicotine on multiple signaling molecules and other regulatory proteins in human DCs to elucidate the molecular basis of the inhibition of DC maturation and function by CSE and nicotine. Maturation of monocyte-derived DCs was induced with the TLR3-agonist poly I:C or with the TLR4-agonist lipopolysaccharide, in the absence or presence of CSE or nicotine. Reverse-phase protein microarray was used to quantify multiple signaling molecules and other proteins in cell lysates. Particularly in poly I:C-matured DCs, cigarette smoke constituents and nicotine suppressed the expression of signaling molecules associated with DC maturation and T cell stimulation, cell survival and cell migration. In conclusion, constituents of tobacco smoke suppress the immunogenic potential of DCs at the signaling pathway level.

Electronic cigarette vapour moderately stimulates pro-inflammatory signalling pathways and interleukin-6 production by human monocyte-derived dendritic cells

“…This resulted in 1% ECVE containing approximately 12 μg/ml nicotine and 3% ECVE containing 36 μg/ml nicotine. This is similar to the nicotine concentrations in 0.5-3% cigarette smoke extract (CSE) used in previous studies (Alkhattabi et al 2018).…”

“…RPPA was performed as described previously (Alkhattabi et al 2018;Negm et al 2014). We had previously confirmed that the detection of signalling molecules by RPPA gave results consistent with those obtained by western blotting (Negm et al 2014).…”

“…The effects of E-cigarettes on the human immune system are not fully elucidated; in particular, the effects of ECVE on human DCs have not been investigated previously although numerous studies have shown deleterious (and mainly immunosuppressive) effects of CS on DCs (Alkhattabi et al 2018;Arellano-Orden et al 2016;Givi et al 2016;Guinet et al 2004;Kroening et al 2008;Le Rouzic et al 2016;Liao et al 2015;Mortaz et al 2009;Guinet 2003, 2006;Nouri-Shirazi et al 2007;Robbins et al 2004Robbins et al , 2008Stampfli and Anderson 2009;Vassallo et al 2005). DCs are professional antigen presenting cells that link innate and adaptive immunity; therefore, due to the importance of DCs within the immune system, the aim of the present study was to investigate the effects of ECVE on the biological behaviour of DCs in vitro using human monocyte-derived DCs.…”

“…The maturation of human monocytederived DCs (moDCs), and their ability to stimulate Th1 and Th17 cells, is also suppressed by CSE (Kroening et al 2008;Le Rouzic et al 2016;Vassallo et al 2005). We have shown that CSE treatment of human moDCs reduced their expression of pro-inflammatory signalling molecules (Alkhattabi et al 2018). Although numerous chemicals within CS affect immune cells (Stampfli and Anderson 2009), nicotine is the main addictive component and has well-documented suppressive effects on IL-12 production and Th1 stimulation by human moDCs and mouse bmDCs, promoting instead Th2 responses (Guinet et al 2004;Guinet 2003, 2006;Nouri-Shirazi et al 2007).…”

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

“…MAM, Poly I:C, LBN) have not yet been assessed. However, considering interactions between the immune system and nicotine [172,173], this is an interesting area of future research.…”