Nicotine modulates the immunological function of dendritic cells through peroxisome proliferator-activated receptor-γ upregulation

Cell Immunol. 2012;274(1-2):26-33. doi: 10.1016/j.cellimm.2012.02.007. Epub 2012 Feb 28.


We examined the effects of nicotine on differentiation and function of monocyte-derived human dendritic cells (DCs). NiDCs, which were the DCs differentiated in the presence of nicotine, showed lower levels of CD1a. Secretion of IL-12 and TNF-α by lipopolysaccharide (LPS)-stimulated NiDCs was significantly suppressed compared to monocyte-derived DCs grown without nicotine. NiDCs displayed a diminished capacity to induce allogeneic T cell proliferation with a reduced production of IFN-γ, and maintained/enhanced LPS-mediated expression of coinhibitory molecules. Interestingly, NiDCs enhanced the expression of nuclear receptor peroxisome proliferator-activated receptors γ (PPAR γ), which has immunomodulatory properties. Expression of PPAR γ and PPAR γ-target genes was significantly inhibited by pretreatment with d-tubocurarine, antagonist of non-selective nicotinic acetylcholine receptors (nAChR). In addition, reduction of Th1 responses was inhibited after blocking nAChR-mediated signal. These data suggest the effect of nicotine on altering DC immunogenicity by impeding Th1 immunity is partially mediated by upregulation of PPAR γ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Gene Expression Regulation / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / metabolism
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation / drug effects*
  • Monocytes / metabolism
  • Nicotine / pharmacology*
  • Nicotinic Antagonists / pharmacology
  • PPAR gamma / biosynthesis*
  • PPAR gamma / genetics
  • Phenotype
  • Receptors, Nicotinic / metabolism*
  • Smoking / adverse effects
  • Smoking / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Tubocurarine / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation


  • Lipopolysaccharides
  • Nicotinic Antagonists
  • PPAR gamma
  • Receptors, Nicotinic
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Nicotine
  • Interferon-gamma
  • Tubocurarine