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

Alkhattabi, Nuha; Todd, Ian; Negm, Ola; Tighe, Patrick J.; Fairclough, Lucy C.

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 signalling 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.

Citation

Alkhattabi, N., Todd, I., Negm, O., Tighe, P. J., & Fairclough, L. C. (2018). Tobacco smoke and nicotine suppress expression of activating signaling molecules in human dendritic cells. Toxicology Letters, 299, 40-46. https://doi.org/10.1016/j.toxlet.2018.09.002

• Journal Article Type: Article
• Acceptance Date: Sep 11, 2018
• Online Publication Date: Sep 15, 2018
• Publication Date: Dec 15, 2018
• Deposit Date: Sep 21, 2018
• Publicly Available Date: Sep 16, 2019
• Journal: Toxicology Letters
• Print ISSN: 0378-4274
• Electronic ISSN: 1879-3169
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 299
• Pages: 40-46
• DOI: https://doi.org/10.1016/j.toxlet.2018.09.002
• Keywords: Dendritic cell; Tobacco smoke; Nicotine; Protein array; Signalome; Autoimmunity
• Public URL: https://nottingham-repository.worktribe.com/output/1098904
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0378427418318757
• Additional Information: This article is maintained by: Elsevier; Article Title: Tobacco smoke and nicotine suppress expression of activating signaling molecules in human dendritic cells; Journal Title: Toxicology Letters; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.toxlet.2018.09.002; Content Type: article; Copyright: © 2018 Elsevier B.V. All rights reserved.
• Contract Date: Sep 25, 2018