The immunosuppressive effects of nicotine during human mixed lymphocyte reaction

Hideo K. Takahashi, Hiromi Iwagaki, Ryosuke Hamano, Toru Kanke, Keyue Liu, Hiroshi Sadamori, Takahito Yagi, Tadashi Yoshino, Noriaki Tanaka, Masahiro Nishibori

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Cell-to-cell interaction through binding intercellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 on monocytes and their ligands on T-cells plays roles in cytokine production and T-cell proliferation. Interleukin (IL)-18, which is elevated in the plasma during acute rejection after organ transplantation, induces the expression of ICAM-1, B7.1, B7.2 and CD40, production of interferon (IFN)-γ and IL-12 and proliferation of lymphocytes during human mixed lymphocyte reaction. Nicotine is known to inhibit the production of pro-inflammatory cytokines from macrophages through the stimulation of nicotinic acetylcholine receptor α7 subunit. In the present study, we examined the effect of increasing concentrations ranging from 0.1 to 100 μM of nicotine on the expression of ICAM-1, B7.1, B7.2 and CD40, production of IFN-γ and IL-12 and proliferation of lymphocytes during mixed lymphocyte reaction treated with IL-18 at 100 ng/ml for 48 h. Nicotine inhibited the expression of adhesion molecules, cytokine production and lymphocyte proliferation. The IC50 values of nicotine for inhibition of the IL-18-enhanced ICAM-1 expression, IFN-γ production and proliferation were 1, 1 and 2 μM, respectively. A non-selective and a selective antagonist for nicotinic acetylcholine receptor α7 subunit, mecamylamine and α-bungarotoxin abolished the effects of nicotine. The actions of nicotine might depend on stimulation of nicotinic acetylcholine receptor α7 subunit. Nicotine induced prostaglandin E2 production during mixed lymphocyte reaction. The inhibitors of cyclooxygenase (COX)-2 and protein kinase A (PKA) at 100 μM inhibited the actions of nicotine, suggesting that the endogenous prostaglandin E2 might be, at least, partially involved the actions of nicotine.

Original languageEnglish
Pages (from-to)69-74
Number of pages6
JournalEuropean Journal of Pharmacology
Volume559
Issue number1
DOIs
Publication statusPublished - Mar 15 2007

Keywords

  • Interleukin-18
  • Monocytes
  • Nicotine
  • Prostaglandin E

ASJC Scopus subject areas

  • Pharmacology

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